A Comprehensive Review on the Screening Models For

Deeksha Gupta*, Vishal Singh, Dakshina Gupta

Masters in Pharmacy(Pharmacology), Advance Institute of Biotechnology and Paramedical Sciences, Naramau, Kanpur, Uttar Pradesh, 209217.

Abstract: Background: The frequency of diabetes all over the globe has grown exotically over the recent past decades, and the vogue will continue for the anticipated future. The development of micro- and macro vascular complications is the dominant concern related to diabetes, whose contribution is highly proportional to the morbidity and mortality of the population with the disease. Advancement of the disease from pre- diabetic state to overt diabetes and the development of complexity transpire over many years. Reckoning of interventions crafted to delay or prevent disease amelioration or complexity in humans also takes years and desires impregnable resources.

Objective: None the less, for an animal model to have more convenience to the study of diabetes, the features of the animal model should portray the patho-physiology and natural history of diabetes or the model should flourish the complications of diabetes with an etiology congruent to that of the human condition. Use of the suitable animal model based on these homogeneities can provide much needed data on patho-physiological mechanisms operative in human type 2 diabetes mellitus.

Methods: A literature search was overseen by serving different keywords like "Type-II Diabetes Mellitus", " Anti-diabetic ", "In-vitro models" and "In-vivo models". The search was made to order by implementing convenient filters with a desire to fetch the best suited articles to meet the objective of this review article.

Result: There are different research and review papers based on the anti-diabetic screening models for the determination of anti-diabetic activity of new drug molecules.

Keywords: Type 2 diabetes mellitus; animal models; rodents; Insulin; Glucose

1. INTRODUCTION: highlighted by insulin hindrance and a propelled crumbling in pancreatic beta-cell work combined Type 2 diabetes mellitus is an interminable with blasting hyper-glycaemia. Flawed beta cell metabolic sickness that happen with glitch in work happens somewhat past and can be track emission and activity of insulin. An up hurled down in personages with fasting as well as post- pace of basal hepatic glucose creation with hyper- prandial glucose levels been hindered generally insulinemia essentially come out with fasting named as "Pre-Diabetics" [5]. Notwithstanding hyperglycemia. Debilitated abrogation of hepatic hereditary inclination, up development of type 2 glucose creation by insulin and devalued insulin- diabetes mellitus in advances in people in the skirt intervened glucose take-up by muscle conduce of mature age, corpulence, cardiovascular malady nearly to postprandial hyperglycemia after a and a lacking physical work [2]. . supper [1]. Type 2 diabetes mellitus is a disease

JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 15

Fig(1): Possible risk factors leading to type2 diabetes mellitus

The patho-physiology of type 2 diabetes mellitus treatments for the administration of type 2 [Fig 3] is multifaceted and incorporates insulin diabetes mellitus incorporate incretin-based discharge from pancreatic islet cells, insulin agents,which act by focusing on huge numbers of obstruction in fringe tissues, and insufficient the key patho-physiologic procedures in type 2 concealment of glucagon creation. These diabetes mellitus, including upgrading insulin procedures bring about lacking take-up, capacity, discharge and restraining glucagon creation [8]. and removal of ingested glucose joined by raised hepatic creation of glucose and hyperglycemia. Proper test models are basic instruments for Loss of beta-cell mass in the pancreatic islets can understanding the atomic premise, patho- advance to a clinically huge degree even, with the beginning of the vascular and neural sores, end goal that at the hour of conclusion of type 2 activities of helpful operators and hereditary or diabetes mellitus, a noteworthy number of cells ecological impacts that expansion the dangers of may as of now be lost. type 2 diabetes. Among the creature models accessible, those created in rodents have been Numerous qualities have been recognized that are read most completely for reasons, for example, engaged with the advancement of type 2 diabetes short age time, acquired hyperglycaemia or mellitus, expanding our comprehension of the potentially heftiness in specific strains and patho-physiology of type 2 diabetes mellitus and monetary contemplations [26] . offering potential new treatment options.Newer

JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 16

Fig(2): Plasma glucose, insulin, and glucagon profiles in response to ingestion of a carbohydrate meal in normal individuals [35].

Fig(3): Type 2 diabetes mellitus Patho-Physiology [6].

JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 17

© 2020 JETIR July 2020, Volume 7, Issue 7 www.jetir.org (ISSN-2349-5162) Creature models permit investigation of the patho-physiology against diabetic medications and these are as per the of sickness, and manage the cost of a way to contemplate the following. hidden biochemical and sub-atomic natural systems. While they can't be utilized altogether as a substitute for the 3.1.1 Chemical Induced Diabetes Models investigation of human diabetes, they permit investigation of angles which can't morally be considered in the patient [4]. Type 2 diabetes Mellitus is instigated by means of a Diabetes examine in people is ruined by clear moral concoction specialist infused to the creature. The most widely contemplations, as affectation of illness is carefully recognized pharmacological model for diabetes in rodents impermissible in human. Creature models of diabetes are and sheep is the organization of streptozotocin (STZ). It is for along these lines incredibly helpful and invaluable in the most part utilized as a device for clarifying components biomedical investigations as they offer promising new which result from acceptance of the malady straightforwardly perceptiveness into human diabetes [2]. in the test creature [4].

2. MATERIAL AND METHODS Possible models that lay under the aforesaid method are:

A writing search was led on different database sources with  Neonatal Streptozotocin model of Type 2diabetes the assistance of the mix of various watchwords: Against mellitus diabetic model, In-vitro, In-vivo models of type 2 diabetes  Low dose STZ with high fat diet-fed rat model mellitus movement. The pursuit was redone by applying the  Nicotinamide -Streptozotocin (NAD-STZ) induced fitting channel in order to get the most pertinent articles to diabetic model meet the goal of this survey. The different quantities of papers  Gold thioglucose obese diabetic mouse are available on the counter diabetic model for the recently orchestrated medications to decide their hostile to diabetic action.

3.1.1.1 Neonatal Streptozotocin model of Type 2 3. TYPES OF MODELS FOR ANTI- diabetes mellitus DIABETIC ACTIVITY

Neonatal rodents STZ in portion of 80-100 mg/kg intra After the debilitating writing review, we have seen that there peritonially during childbirth or inside five days following is 'n' number of models present in which, some of them are birth is infused in the rodents. Serious pancreatic β cell not being used these days due to troubles in their demolition causes decline in insulin stores, increment in methodology or on account of poor outcome, while there are glucose levels. β cells of neonatal rodents incompletely some different models present which give great outcomes in recover because of high development thus the rodents become a limited capacity to focus time. So essentially, these models normo glycemic by 3 weeks old enough [20]. are either utilized in the lab with the assistance of instruments and synthetic substances while in certain models, creature prerequisite is fundamental. Based on the philosophy, we 3.1.1.2 Low dose STZ with high fat diet-fed rat isolate hostile to diabetic models concerning In-vitro or In- model vivo. The creature isn't required for in-vitro models, while In- Vivo models, creatures are required for the improvement of This model mirrors the normal history and metabolic hyperglycaemia and by the assistance of In-vivo model, we attributes of human sort 2 diabetes [25]. High-vitality diet of decide the movement of recently blended medication or atom. 20% sucrose 10% grease and single infusion of STZ (30 The motivation behind the survey is to talk about just the in- mg/kg body weight) Incites type-2 diabetes following 4 a vivo models for screening of type 2 diabetes mellitus. In this month and a half by adjustment of quality articulation in way, these models are isolated into two gatherings which are Sprague–Dawley rodents [9,10]. The high glucose-fat eating as per the following. regimen is allowed for about a month and a half and afterward the low portion of streptozotocin is given intra peritonially 3.1 In-vivo Models [27].

The term in-vivo legitimately shows the assessment of 3.1.1.3 Nicotinamide -Streptozotocin (NAD- medications in a living being, and assessment of the counter STZ) induced diabetic model diabetic medications is inadequate without utilizing In-vivo model since diabetes is an infection which happens in the Type 2 diabetes mellitus was prompted by a solitary intra inward condition of the body and structures injuries in people. peritoneal infusion of STZ (65mg/kg) and NAD (110mg/kg) Type 2 diabetes mellitus instigated by the pharmacological, [after 10 minutes] to rodents [28]. NAD is a cancer prevention careful and by physiological control in the creature. agent which applies defensive impact on the cytotoxic Typically, a large portion of the trials are done in rodents [11]. activity of STZ by rummaging free radicals and makes just The principle preferred position of these models is that we can minor harm pancreatic beta cell mass delivering type-2 decide the real enemy of diabetic action of medication diabetes. Accordingly, this model is viewed as a worthwhile planning, however it is a period taking procedure which is instrument for examination of insulinotropic specialists in the likewise an inconvenience of these models. Hostile to diabetic treatment of type2 diabetes mellitus [3]. movement of medication planning likewise relies on the kind of models we select for the assurance of against diabetic property. In-vivo models are utilized for assessment of JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 18

© 2020 JETIR July 2020, Volume 7, Issue 7 www.jetir.org (ISSN-2349-5162) 3.1.1.4 Goldthioglucose obese diabetic mouse bringing about ketosis and the necessity of exogenous insulin to continue life [15]. Type 2 diabetes with heftiness is actuated in mice by goldthioglucose (GTG) (150-350 or 200 mg/kg, ip)injection. Mice step by step create stoutness, hyperinsulinaemia, 3.1.3.1 The fatty Zucker (Zucker diabetic fatty hyperglycaemia, insulinresistance over a time of 16-20 wk (ZDF) after GTG infusion [29]. The GTG is shipped specifically tothe cells of ventro average nerve center (VMH) and causes The rodent has been esteemed as a model of corpulence, as necrotic injuries, which consequently is answerable for the the qualities of the model are portrayed as hyperglycemia, advancement of hyperphagia and heftiness. It likewise shows early hyperinsulinemia, fasting hyperglycemia, anomalous expanded body lipid and hepatic lipogenesis and triglyceride glucose resistance, hyperlipidemia, gentle hypertension. The secretion,increased fat tissue lipogenesis and diminished ZDF rodent conveys the Lepfa or Ob-Rfa transformation, glucose digestion in muscle, variations from the norm that are which is regularly alluded to as just fa [17]. subjectively like hereditarily corpulent mice.

3.1.3.2 The obese spontaneously hypertensive 3.1.2 Hormone induced diabetes Models rat (SHORB),

Hyperglycemia and glucosuria in constrained took care of The fat phenotype results from a transformation of leptin rodents treated with cortisone was seen in corticosteroid receptor assigned fak. SHORB is a valuable model to initiated diabetes [11]. In the guinea pigs and in the hares, trial comprehend the connection of the different metabolic corticoid diabetes could be gotten without constrained taking anomalies [18]. The heftiness transformations in the mouse care of [12,13]. In the rodents, the adrenal cortex, animated ob (hefty) and db (diabetic) are change in the leptin basic by corticotrophin, has the ability to emit measures of steroids quality (ob) and transformation in the leptin receptor quality which incite steroid diabetes [14]. (db). The large hyperglycemic disorder showed by these mice demonstrates different likenesses to type 2 diabetes mellitus. 3.1.3 Genetic and Spontaneous models Insulin obstruction, wrong hyperglycemia, weakened glucose resistance just as expanded insulin discharge at long last prompting b cell fatigue are found in these models. Anyway age, sexual orientation, and upkeep conditions are accounted for to influence the phenotype of these mice.

3.1.3.3 The Spontaneously diabetic KK mice

They are accounted for to have moderate heftiness, polyphagia, polyurea, persitent glycosuria, glucose bigotry, moderate hyperglycemia, hyperlipidemia, insulin opposition of fringe tissues and hyperinsulinemia. The diabetic attributes of KK mice and the variation KKAy are returned to ordinary following 40 weeks old enough [19].

3.1.4 Dietary or nutrition induced type 2 diabetic models

A portion of the creature models exist in which diabetes is instigated neither by synthetic concoctions nor by hereditary imperfection. Sand rodent, Tuco-Tuco and Spiked mouse are significant models of healthfully actuated corpulence and Fig(4): Genetic Programming of development of Metabolic type 2 diabetes [21]. Syndrome [4] 3.1.4.1 Sand rat (Psammomys obesus)

Spontaneous models of type 2 diabetes mellitus are highly It is a model of healthfully actuated Sort 2 diabetes mellitus. heterogeneous. At one end of the spectrum there is a mild Psammomys is inclined to creating hyperinsulinemia, hyperglycemia associated with obesity and hyperinsulinemia. hyperglycemia and weight when moved to a high-vitality diet, At the other extreme, animal models of Type 2 diabetes likewise essential insulin obstruction is an animal varieties mellitus can develop a severe form of diabetes mellitus with portrayal of Psammomys [22,23]. In any case, the possibility extensive b cell degeneration, occasionally resulting in to become diabetic declines with age. In Psammomys of ages ketosis models of type 2 diabetes mellitus are profoundly 1 a year, kept up on a low-vitality diet from weaning and heterogeneous. Toward one side of the range there is a moved at various ages to a high-vitality diet [16], the mellow hyperglycemia related with weight and affectability to the advancement of diabetes mellitus hyperinsulinemia. At the other outrageous, creature models of increments from weaning to a pinnacle of around 5 months Type 2 diabetes mellitus can build up an extreme type of old enough and diminishes from there on. diabetes mellitus with broad b cell degeneration, incidentally JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 19

© 2020 JETIR July 2020, Volume 7, Issue 7 www.jetir.org (ISSN-2349-5162) 3.1.5 Surgical type 2 diabetic models Mohammed (Unpublished) utilized this strategy to instigate hyperglycaemia in wistar rodents. The strategy was found to This strategy comprises of complete or halfway create a generally fluctuating degree of hyperglycaemia when pancreatectomy in creatures utilized for the enlistment of type contrast with alloxan enlistment technique [46]. 1 or type 2 diabetes, separately. Historically,the diabetic pooch model found by Oskar Minkowski through careful 4. END-POINTS TO STUDY ANIMAL complete pancreatectomy has been viewed as the main MODELS OF DIABETES creature model of diabetes and is once in a while now utilized for the examination. Be that as it may, halfway When testing treatments in creature models of diabetes, the pancreatectomy and additionally mix strategies on creatures most widely recognized end-purpose of estimation is blood especially non rodents are on occasion used in the diabetes glucose focuses. It ought to be called attention to that various examination for some particular investigations as portrayed species will in general have diverse blood glucose focuses underneath. than people, and along these lines, definitions for diabetes in people ought not really be applied to creatures . Location of 3.1.5.1 VMH dietary obese diabetic rat model glucose in the pee can likewise be estimated as an indication of diabetes. Be that as it may, in a mind boggling ailment, for It has been created by trial careful control of hereditarily example, diabetes, opposite end-focuses ought to be typical creatures without the decrease in pancreatic beta cell researched. Different endpoints will rely upon the putative mass taking after sort 2 diabetes by joining reciprocal component of the medication and the model being utilized. electrolyte sore of VMH and taking care of high fat and high The time course of the malady ought to likewise be sucrose consumes less calories named as VMH dietary fat painstakingly viewed as when considering end-purposes of an rodents [24]. It is described by stamped heftiness, hyper- examination. A few models of type 2 diabetes show beta cell insulinaemia, hyper-triglyceridaemia, insulin obstruction, development and hyper insulinaemia before resulting beta weakened glucose resilience, moderate tosevere fasting cell disappointment, and the phase of sickness may influence hyperglycaemia and imperfect guideline of insulin secretory the parameters that are being estimated. Notwithstanding, it reaction regardless of very high insulin secretory limit. It is ought to be noticed that in models of type 2 diabetes, the fascinating that huge hyperphagia is seen in spite of expanded system of the medication bringing down blood glucose levels leptin levels (leptin obstruction) in these VMH sore rodents. may incorporate weight reduction [36]. Glucose resilience 3.1.5.2 Non obese partial pancreatectomized tests are frequently used to research beta cell work. This can diabetic animals permit impeded glucose resistance to be distinguished, which is for the most part viewed as a pre‐diabetic state. This is Incomplete pancreatectomy in creatures proceeded as 70 or frequently done after a short-term quick, in spite of the fact 90 percent (typically 90%) analyzation of pancreas has been that it ought to be noticed that it has been proposed that such accounted for in different creature species for the most part in a drawn out quick might be unseemly in mice as it prompts a hounds, pigs, bunny and furthermore rodents [30,31,32]. It metabolic pressure and improves insulin activity [37], and doesn't cause extreme type of diabetes and is portrayed by subsequently, a 6 h quick might be ideal. There are no away moderate hyperglycaemia with neither decrease in body from of impeded glucose resistance for rodents, yet in weight nor decrease in plasma insulin levels. The 90 percent ordinary nondiabetic mice, an IPGTT arrives at a top at 15– in part pancreatectomized rodents likewise demonstrate 30 min; and by 120 min, the blood glucose ought to be imperfection or particular impedance to glucose invigorated near the pattern esteem [38]. Serum insulin or c‐peptide levels insulin discharge however stay unblemished to other insulin can be estimated to show beta cell work, albeit high insulin secretogogues like neonatal STZ rodents. This finding from levels can in a roundabout way demonstrate insulin these fractional pancreatectomized creatures bolsters the obstruction. An insulin resilience test can be completed as a thought that just decrease in pancreatic beta cell mass itself surmised proportion of insulin obstruction, or a progressively may not be liable for the glucose narrow mindedness as rich hyperinsulinaemic–euglycaemic brace can be done [39]. observed in neonatal STZ rodents [33]. These fractional It ought to be noticed that proxy proportions of insulin pancreatectomized creatures are accounted for to create affectability, for example, the homeostasis model file of hyperglycaemia and insulin opposition. Improvement of insulin opposition (HOMA‐IR) can be utilized in rodents, hyperglycaemia and insulinresistance is seen by organization despite the fact that species explicit changes may should be of insulinor phlorizin, an inhibitor of renal glucose re made [40]. It ought to likewise be noticed that in people, type assimilation [34]. 2 diabetes will in general present sometime down the road, and in this manner, the utilization of more established mice 3.1.6 Oral glucose loading animal model when contemplating this condition ought to be thought of.

5. SELECTION OF APPROPRIATE MODEL This technique is frequently alluded to as physiological enlistment of diabetes mellitus on the grounds that the blood FOR TYPE 2 DIABETES MELLITUS glucose level of the creature is fleetingly expanded with no harm to the pancreas. In the clinical setting, it is known as An assortment of creature models of type 2 diabetes are Glucose resilience testing (GTT): a standard system regularly portrayed over, each with their own attributes. There are a few utilized for the finding of marginal diabetic patients. In this unique purposes that these models of diabetes could be strategy, the creatures are fasted for the time being, at that utilized for including pharmacological testing, investigations point oral glucose load (1-2.5 g/kg body weight) is given and of hereditary qualities and understanding infection systems. blood glucose level is observed over some stretch of time. The decision of model will rely upon the motivation behind Typically bunnies or male rodents are utilized. Etuk and the investigation. For instance, on account of JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 20

© 2020 JETIR July 2020, Volume 7, Issue 7 www.jetir.org (ISSN-2349-5162) pharmacological testing, the putative component of the medication being tried will be instrumental in picking a 7. REFERENCES: proper creature model [41]. In type 2 diabetes, it is essential to consider the systems basic the hyperglycaemia and whether 1. Ralph A. DeFronzo et al, Pharmacologic Therapy for Type this is applicable to your examination. These systems can 2 Diabetes Mellitus 1999 American College of Physicians– incorporate insulin opposition or potentially beta cell American Society of Internal Medicine, 17 August 1999 • disappointment. To be sure, to decide if a medication Annals of Internal Medicine • Volume 131 • Number 4 intercession can improve manifestations in some random model may rely upon whether beta cells have fizzled. 2. Animal models in type 2 diabetes research: An overview Creature models of type 2 diabetes can be partitioned into by K. Srinivasan & P. Ramarao Department of Pharmacology those that are stout and those that are nonobese. Most of type & Toxicology, National Institute of Pharmaceutical 2 diabetes models are stout, by either hereditary or dietary Education &Research (NIPER), Mohali, India methods. Be that as it may, this normally accompanies an assortment of related pathologies, for example, dyslipidaemia 3. Pellegrino M, Christopher B, Michelle M, et al. Diabetes and artherosclerosis. In spite of the fact that these co‐ 1998; 47: 224-230 morbidities are basic in certain people with type 2 diabetes, it just speaks to a bit of the diabetic populace. Likewise, it ought 4. Ingle DJ, Li CH, Evans HM (1946) The effect of to be noticed that not every single creature model of diabetes adrenocorticotropic and strains create diabetic inconveniences [42], so care ought hormone on the urinary excretion of sodium, chloride, to be taken in picking a suitable model if the end‐point of the potassium, nitrogen and glucose in normal rats. examination is to research diabetic difficulties, for example, Endocrinology 39:32–39 nephropathy or neuropathy [43,44,45].

6. CONCLUSION 5.L H Bösenberg & D G van Zyl (2008) The mechanism of action of oralantidiabetic drugs: A review of recent literature, A large number of the creature models depicted obviously Journal of Endocrinology, Metabolism and Diabetes of South share comparative trademark highlights of type 2 diabetes and Africa, 13:3, 80-88, DOI: 10.1080/22201009.2008.10872177 have permitted experimentation that would be unimaginable in people. None of the realized single species is actually 6. Defronzo RA. Diabetes. 2009 Apr;58(4):773-95 Inzucchi proportionate to human diabetes, yet each model go about as SE, Sherwin RS in: Cecil Medicine 2011cchi SE, Sherwin RS basic apparatus for exploring hereditary, endocrine, in: Cecil Medicine 2011 metabolic, morphologic changesand hidden aetiopathogenic instruments that could likewise work during the advancement 8. Craig W. Spellman, DO, PhD, Spellman • Pathophysiology of type 2 diabetes in people. Subsequently, care must be taken of Type 2 Diabetes: Targeting Islet Cell Dysfunction JAOA • in understanding and extrapolation of the outcomes acquired Supplement 2 • Vol 110 • No 3 • March 2010 • S7 from these creature models to people. In the screening project of against diabetic mixes, itis especially critical to take note 9. Hui JW, Yuan XJ, Shen W, et al. Asia Pacific Journal of of that some creature models are more qualified to screen Clinical Nutrition 2007; 16 (1, suppl): 412-417. specific class of hostile to diabetic mixes. Since beginning restorative science crusades and screening, for the most part 10. Srinivasan K, Viswanad B, Lydia Asrat, et al. require the testing of numerous mixes in the mechanical Pharmacological Research 2005; 52: 313–320. research condition, utilization of littler creature models, for example, mice, will diminish the cost of delivering test 11. Ingle DJ (1941) The production of glycosuria in the materials while some propelled adequacy contemplates or normal rat by means of 17-hydroxy-11- toxicological assessments which require obtrusive dehydrocorticosterone. Endocrinology 29:649–652 methodology and huge blood andtissue tests, might be encouraged by utilizing creatures with huge body size, for 12. Hausberger FX, Ramsay AJ (1953) Steroid diabetes in example, rodent or other non rodents. Further, the choice of guinea pigs. Effect of cortisone administration on blood- and specific creature model is especially relying upon the urinary glucose, nitrogen excretion, fat deposition, and the specialist's decision whether to utilize innate or outbred, islets accessibility of specific strain, point of logical technique, kind of Langerhans. Endocrinology 53:423–435 of medication being looked for, institutional money related and office assets in the sort 2 diabetes inquire about and 13. Abelove WA, Paschkis KE (1954) Comparison of the pharmaceutical medication disclosure and advancement diabetogenic action of cortisone and growth hormone in program. In spite of the fact that there are a few constraints different species. Endocrinology 55:637–654 like cost, down to earth troubles, extraordinary consideration and moral contemplations related with the utilization of 14. Ingle DJ, Li CH, Evans HM (1946) The effect of enormous/non rat creature species (pigs, hounds and non adrenocorticotropic hormone on the urinary excretion of human primates), the definite examinations in these diabetic sodium, chloride, potassium, nitrogen and glucose in normal creature species are direly required for better comprehension rats. Endocrinology 39:32–39 of the sickness components in much intently comparative human circumstance just as for finding more up to date targets 15. Pickup JC and Williams G, editors. Textbook of diabetes. and medications for the treatment of type 2 diabetes and its 3rd Ed, USA: Blackwell Science Ltd 2003. entanglements.

JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 21

© 2020 JETIR July 2020, Volume 7, Issue 7 www.jetir.org (ISSN-2349-5162) 16. Ziv E, Shafrir E, Kalman R, Galer S, Bar-On H. Changing 28. International Journal of Advances in Pharmaceutical patterns of prevalence of insulin resistance in Psammomys Sciences 1 (2010) 75-85 Studies on the anti-diabetic and obesus, a model of nutritionally-induced Type 2 diabetes. hypolipidemic potentials of mangiferin (Xanthone Metabolism 1999;48:1549-54. Back to cited text no. 3 Glucoside) in streptozotocin-induced Type 1 and Type 2 [PUBMED] diabetic model rats by B Dineshkumar, Analava Mitra1, M Manjunatha. 17. Corsetti JP, Sparks JD, Peterson RG, Smith RL, Sparks CE. Effects of dietary fat on the development of non-insulin 29. Le Marchand Brustel Y, Jeanrenaud B, Freychet P. Insulin dependant diabetes mellitus in obese Zucker diabetic fatty binding and effects in isolated soleus muscle of lean andobese male and female rat. Atherosclerosis 2000;48:231-41 mice. Am J Physiol 1978; 234: E348-58.

18. Ishizuka T, Ernsberger P, Liu S, Bedol D, Lehman TM, 30. McNeil JH. Experimental models of diabetes. Florida, Koletsky RJ. Phenotypic consequences of a nonsense USA:CRC Press LLC; 1999. mutation in the leptin receptor gene (fak) in obese spontaneously hypertensive Koletsky rat (SHORB). J Nutr 31. Ibanez-Camacho R, Meckes-Lozaya M, Mellado- 1998;128:2299-306. CamposV. The hypoglycemic effect of Opuntia strepto can the studied in different animal experimental models.J 19. Suto JS, Matsuura S, Imamura K. Genetic analysis of non- Ethnopharmacol 1983; 7 : 175-81. insulin dependent diabetes mellitus in KK and KK-Ay mice. Eur J Endocrinol 1998;139:654-61. 32 .Sasaki S, Nio Y, Hirahara N, Sato Y, Inoue Y, Iguchi C, etal. Intraperitoneally implanted artificial pancrease with 20. Okamato H. Regulation of proinsulin synthesis in transkaryotic beta-cells on micro carrier beads in a pancreatic islets and a new aspect to insulin dependant diffusionchamber improves hyperglycemia after diabetes. Mol Cell Biochem 1981;37:43-61. 90%pancreatectomy in rats. In Vivo 2000; 14 : 535-41

21. Shafrir E. Diabetes in animals: Contribution to 33. Portha B, Giroix M-H, Serradas P, Morin L, Tormo M- theunderstanding of diabetes by study of its etiopathology A,Bailbe D. Cellular basis for glucose refractoriness of inanimal models. In: Porte D, Sherwin RS, Baron A, pancreatic B-cells in non insulin dependent diabetes. In:Flatt editors.Diabetes mellitus. NewYork: McGraw-Hill; 2003p. PR, Lenzen S, editors. Insulin secretion andpancreatic B cell 231-55 research. UK: Smith-Gordon, 1994 p.461-72.

22. Shafrir E, Ziv E, Mosthaf L. Nutritionally induced 34. Bonner-Weir S, Trent DF, Weir GC. Partial insulinresistance and receptor defect leading to beta cell pancreatectomy in the rat and subsequent defect in glucose- failure in animal models. Ann NY Acad Sci 1999;892 : 223- induced insulin release.J Clin Invest 1983; 71 : 1544-53 46 35. Unger RH. N Engl J Med. 1971;285(8):443-449.7 23. Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi Copyright 1971 Massachusetts Medical Society. M,Natori T. Spontaneous long-term hyperglycemic rat with diabetic complications, Otsuka Long-Evans TokushimaFatty 36. Knudsen LB (2010). Liraglutide: the therapeutic promise (OLETF) strain. Diabetes 1992; 41 : 1422-8 from animal models. Int J Clin Pract Suppl. 64: 4–11

24. Axen KV, Li X, Fung K, Sclafani A. The VMH- 37. McGuinness OP, Ayala JE, Laughlin MR, Wasserman dietaryobese rat: a new model of non-insulin-dependent DH (2009). NIH experiment in centralized mouse diabetesmellitus.Am J Physiol 1994; 266 : R921-8 phenotyping: the Vanderbilt experience and recommendations for evaluating glucose homeostasis in the 25. Combination of high-fat diet-fed and low-dose mouse. Am J Physiol Endocrinol Metab 297: E849–E855. streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening: K.SrinivasanB.Viswanad,Lydia 38. Leiter EH (2009). Selecting the ‘right’ mouse model for Asrat,C.L.KaulP.Ramarao Department of Pharmacology and metabolic syndrome and type 2 diabetes research. Methods Toxicology, National Institute of Pharmaceutical Education Mol Biol 560: 1–17. and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Mohali 160 062, Punjab, India 39. Declercq J, Kumar A, Van Diepen JA, Vroegrijk IOCM, Gysemans C, Di Pietro C et al . (2010). Increased +¦− cell 26. Development and application of rodent models for type 2 mass by islet transplantation and PLAG1 overexpression diabetes Desu Chen Ming‐Wei Wang causes hyperinsulinemic normoglycemia and hepatic insulin resistance in mice. Diabetes 59: 1957–1965. 27. Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low- 40. Mather K (2009). Surrogate measures of insulin dose streptozotocin Tabusi Manaer, LanYu, YiZhang, Xue- resistance: of rats, mice, and men. Am J Physiol Endocrinol JunXiao, Xin-Hu, Nabia Department of Pharmacology, Metab 296: E398–E399. Xinjiang Medical University, Urumqi 830011, China Xinjiang Uyghur Autonomous Region Institute for Food and 41. Review on Use of Animal Models in Diabetes Research Drug Control, Urumqi 830004,. by Aileen JF King, Diabetes Research Group, King’s College London, London, UK DOI:10.1111/j.1476- 5381.2012.01911.x JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 22

42. Brosius FC III, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB et al . (2009a). Mouse models of diabetic nephropathy. J Am Soc Nephrol 20: 2503–2512.

43. Breyer MD, Bottinger E, Brosius FC, Coffman TM, Fogo A, Harris RC et al . (2005). Diabetic nephropathy: of mice and men. Adv Chronic Kidney Dis 12: 128–145.

44. Sullivan KA, Hayes JM, Wiggin TD, Backus C, Su OS, Lentz SI et al . (2007). Mouse models of diabetic neuropathy. Neurobiol Dis 28: 276–285.

45. Brosius FC III, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB et al . (2009b). Mouse models of diabetic nephropathy. J Am Soc Nephrol 20: 2503–2512.

46. Animals models for studying diabetes mellitus Etuk, E.U Department of Pharmacology, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigera

JETIR2007003 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 23