Dysglycemia and Dyslipidemia Models in Nonhuman Primates: Part I. Model of Naturally Occurring Diabetes

Abstract

Insulin-resistant diabetes (Type 2 diabetes mellitus, T2DM) is one of the main comorbidities of obesity and is the most common form of diabetes. T2DM and obesity dynamically influence each other and often escalate patients' other health issues. Cardiovascular, renal and other health consequences of obesity and diabetes have been studied for several decades. However, the underlying precise mechanisms and interactions of obesity and insulin-resistant diabetes have yet to be elucidated further. It has been recognized that sustained greater energy intake than expenditure is the main cause of obesity that can potentially lead to insulin resistance and diabetes due to excessive fat accumulation. To better understand the pathophysiology of human obesity and diabetes, nonhuman primate (NHP) models have been used for research to delineate molecular and cellular mechanisms because of the similarity of the metabolic diseases between NHP and humans. Also, NHP models have been well used for testing new novel therapies, which provides critical pre-clinic information for drug discovery. This article summarizes the data collected from a large scale of the naturally occurring diabetes monkeys housed in our facility. Manuscripts for other NHP models, such as diet-induced dyslipidemia and dysglycemia and streptozocin-induced diabetes, developed in our facility will follow lately. Dysglycemia and Dyslipidemia Models in Journal of Diabetes and MetabolismCitation: Wang X, Wang B, Sun G, Wu J, Liu Y, et al. (2015) This article introduces the characteristics of one NHP diabetic model, naturally occurring diabetes, which has been highly valuable for research and treatment of dyslipidemia and dysglycemia [14][15][16][17]. Other NHP models, such as diet-induced dyslipidemia and dysglycemia and streptozocin-induced diabetes, developed in our facility will be introduced lately via other manuscripts. While no single model is necessarily applicable to every dysmetabolic research program and drug discovery, it has been suggested that certain models have great validity. Therefore, if possible, selectively using of those preferable models to achieve the best potential outcome is recommended in order to address the very challenging diseases, obesity and diabetes. Normal and obese/diabetic monkeys housed in our animal center are collected periodically from the monkey farms in China and then raised in our own facility with a normal calorie monkey chow (Beijing Keao Xieli Feed Co., LTD, Beijing, China) enriched with seasonal fruits and vegetables in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) regulations and guidelines [18][19][20]. All the procedures for sample or data collection used in this study were approved by the Institutional Animal Care and Use Committee (IACUC) (Crown Bioscience, Inc., Taicang, Jiangsu province, The People's Republic of China) [18][19][20]. Animal grouping and their general characteristicsAs humans and other great apes (Hominoidea) diverged from Old World m...

The Non-Human Primate in Safety Assessment of a Bifunctional Long-Acting Insulin Analogue

“…The increased sensitivity could possibly be related to the low basal blood glucose levels in NHPs. In cynomolgus monkeys, the normal serum/plasma glucose level is about 3-4 mmol/L, 6,8,9,12 as compared to about 3.5-5 mmol/L in Göttingen minipigs, 4-6 mmol/L in Beagle dogs, 8-10 mmol/L in rats and 3.9-5.6 mmol/L in humans. 13–18 Therefore, relatively small absolute decrements in blood glucose level will correspond to a high percentage decrease; here, for instance, the fall in blood glucose level by 1.4 mM seen in the female after the first dose corresponded to a 36% decrease.…”

“…dose of 3 nmol/kg decreased blood glucose levels by about 35-70% within 15-20 min and a s.c. dose of 0.9 nmol/kg by about 50% within 60 minutes in males and females. 6,8,9 This illustrates that doses should be selected carefully as small increases in dose may be intolerable (ie, a steep dose response curve). In humans it is known that frequent hypoglycaemic episodes weaken the counter-regulatory responses and may therefore increase the incidence and severity of such episodes over time.…”

Dysglycemia and Dyslipidemia Models in Nonhuman Primates: Part III. Type I or II Diabetogenic Effects of Streptozocin

“…Various hyperglycemic animal models have been used in diabetes research, including spontaneously developed, genetically manipulated, diet-induced and drug-caused diabetic models [8][9][10][11][12][13][14][15][16][17]. Nonhuman primates (NHPs) have shown spontaneous dysglycemia and dyslipidemia similar to the progression in humans, which makes them excellent translational models for diabetes and obesity research [12][13][14][15][16][17]. Dysglycemia is a broad term that refers to an abnormality in blood sugar levels, including hypoglycemia or hyperglycemia.…”