Tracking changes of the parameters of glucose-insulin homeostasis during the course of obesity in B6D2F1 mice

Abstract

Obesity is one of the primary causes of type 2 diabetes mellitus (T2DM). To better understand how obesity impairs glucose-insulin homeostasis, we tracked fasting blood glucose and insulin levels and the key components of glucose-insulin homeostasis for 7 months in high fat diet (HFD; 45% fat) fed mice (n ¼ 8). Every 2 weeks we measured body weight, fasting blood glucose and insulin levels, and estimated 5 key rate constants of glucoseinsulin homeostasis using the methods established previously (Heliyon 3: e00310, 2017). Mice gained weight steadily, more than doubling their weights after 7 months (23.6 AE 0.5 to 52.3 AE 1.4 g). Fasting (basal) insulin levels were elevated (221.3 AE 16.7 to 1043.1 AE 90.5 pmol l -1 ) but fasting blood glucose levels unexpectedly returned to the baseline levels (152.8 AE 7.0 to 152.0 AE 7.2 mg/dl) despite significantly elevated levels (216.8 AE 44.9 mg/dl, average of 3 highest values for 8 mice) during the experimental period. After 7 months of HFD feeding, the rate constants for insulin secretion (k 1 ), insulin-independent glucose uptake (k 3 ), and insulin concentration where liver switches from glucose uptake to release (I pi ) were significantly elevated. Insulin-dependent glucose uptake (k 2 ) and rate constant of liver glucose transfer (k 4 ) were lowered but no statistical significance was reached. The novel and key finding of this study is the wide range of fluctuations of the rate constants during the course of obesity, reflecting the body's compensatory responses against metabolic alterations caused by obesity.

Study of blood glucose and insulin infusion rate in real-time in diabetic rats using an artificial pancreas system

“…We are also using a rat APS to develop an accurate and adaptable BGL prediction artificial neural network (ANN) model and to test a new ANNbased algorithm for a closed-loop APS as a proof of concept project. We have previously studied a mathematical model of glucose-insulin homeostasis to estimate insulin secretion, glucose uptake by tissues, and hepatic handling of glucose [29] and tracked changes of the parameters of glucose-insulin homeostasis during the course of obesity in mice [30]. A rat APS may provide insights of the progression of both type 1 and type 2 diabetes.…”

Extra virgin coconut oil (Cocos nucifera L.) intake shows neurobehavioural and intestinal health effects in obesity-induced rats

“…1 Diet quality related to the western pattern is one of the factors that predispose individuals to obesity due to increased consumption of processed foods, high salt, sugar, and fat (total, trans, and saturated) contents, and a reduction in fibre content. 2 Chronic inflammation in obesity has been investigated in recent years as the main cause of metabolic disorders, 3 resulting in an increased risk of developing diabetes, 4 hepatic steatosis, immunological and endocrine changes, 5 and cancers. 6 The low-grade inflammatory response in adipose tissue can lead to an increase in macrophage infiltration and proinflammatory cytokines such as interleukin 1β and TNF-α.…”

“…Chronic inflammation in obesity has been investigated in recent years as the main cause of metabolic disorders, 3 resulting in an increased risk of developing diabetes, 4 hepatic steatosis, immunological and endocrine changes, 5 and cancers. 6 The low-grade inflammatory response in adipose tissue can lead to an increase in macrophage infiltration and proinflammatory cytokines such as interleukin 1β and TNF-α.…”