Abstract
Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.
Highlights
Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals
The current studies were undertaken to characterize the metabolic responses and assess gastric emptying to a mixed meal tolerance test (MMTT) in spontaneously obese cynomolgus monkeys
The reproducibility of the MMTT was robust for the metabolic biomarkers and plasma acetaminophen appearance
Summary
Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The purpose of the test is to measure pancreatic β-cell insulin secretion and glucose tolerance in response to the meal-induced increases in digested nutrients. In condition with impaired insulin secretion such as in insulin-dependent type 1 and type 2 diabetes mellitus (T2DM), the MMTT is used to assess β-cell function and is regarded as more physiological than the glucagon stimulation test (GST), which is a standard measure of endogenous insulin secretion[2,3,4]. MMTT-induced stimulation of insulin release involves an enteroinsular axis via incretin hormones, such as gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), amongst others. These hormones are primarily produced by enteroendocrine cells of the gut and secreted into the blood stream after meal ingestion. Nonhuman primates (NHPs) can naturally become obese and develop T2DM in a manner similar to the onset and progression of T2DM in humans, which makes them excellent models for diabetes and obesity research[15,16,17,18,19,20,21,22,23,24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
