scholarly journals Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in a SHP2-dependent Manner

Diabetes ◽  
2019 ◽  
pp. db180695
Author(s):  
Cheng Dai ◽  
Xinyu Wang ◽  
Yanjun Wu ◽  
Yi Xu ◽  
Shu Zhuo ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Dependent Manner ◽  
Insulin Pathway ◽  
Hepatic Glucose

Glucose homeostasis in rainbow trout fed a high-carbohydrate diet: metformin and insulin interact in a tissue-dependent manner

2011 ◽  
Vol 300 (1) ◽  
pp. R166-R174 ◽  
Author(s):  
S. Polakof ◽  
T. W. Moon ◽  
P. Aguirre ◽  
S. Skiba-Cassy ◽  
S. Panserat
Keyword(s):  
Skeletal Muscle ◽  
Rainbow Trout ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Combined Treatment ◽  
Hypoglycemic Agents ◽  
Dependent Manner ◽  
Metformin Treatment ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Glucose Output

Carnivorous fish species such as the rainbow trout ( Oncorhynchus mykiss ) are considered to be “glucose intolerant” because of the prolonged hyperglycemia experienced after intake of a carbohydrate-enriched meal. In the present study, we use this species to study glucose homeostasis in fish chronically infused with the hypoglycemic agents, insulin, and metformin, and fed with a high proportion of carbohydrates (30%). We analyzed liver, skeletal muscle, and white adipose tissue (WAT), which are insulin- and metformin-specific targets at both the biochemical and molecular levels. Trout infused with the combination of insulin and metformin can effectively utilize dietary glucose at the liver, resulting in lowered glycemia, increased insulin sensitivity, and glucose storage capacity, combined with reduced glucose output. However, in both WAT and skeletal muscle, we observed decreased insulin sensitivity with the combined insulin + metformin treatment, resulting in the absence of changes at the metabolic level in the skeletal muscle and an increased potential for glucose uptake and storage in the WAT. Thus, the poor utilization by rainbow trout of a diet with a high proportion of carbohydrate can at least be partially improved by a combined treatment with insulin and metformin, and the glucose intolerance observed in this species could be, in part, due to some of the downstream components of the insulin and metformin signaling pathways. However, the predominant effects of metformin treatment on the action of insulin in these three tissues thought to be involved in glucose homeostasis remain exclusive in this species.

scholarly journals Knockdown of Neuropeptide Y in the Dorsomedial Hypothalamus Promotes Hepatic Insulin Sensitivity in Male Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4842-4852 ◽  
Author(s):  
Lin Li ◽  
C. Barbier de La Serre ◽  
Ni Zhang ◽  
Liang Yang ◽  
Hong Li ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Neuropeptide Y ◽  
Glucose Homeostasis ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Motor Nucleus ◽  
Hepatic Insulin Sensitivity ◽  
Hepatic Glucose

Recent evidence has shown that alterations in dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) signaling influence glucose homeostasis, but the mechanism through which DMH NPY acts to affect glucose homeostasis remains unclear. Here we report that DMH NPY descending signals to the dorsal motor nucleus of the vagus (DMV) modulate hepatic insulin sensitivity to control hepatic glucose production in rats. Using the hyperinsulinemic-euglycemic clamp, we revealed that knockdown of NPY in the DMH by adeno-associated virus-mediated NPY-specific RNAi promoted insulin’s action on suppression of hepatic glucose production. This knockdown silenced DMH NPY descending signals to the DMV, leading to an elevation of hepatic vagal innervation. Hepatic vagotomy abolished the inhibitory effect of DMH NPY knockdown on hepatic glucose production, but this glycemic effect was not affected by vagal deafferentation. Together, these results demonstrate a distinct role for DMH NPY in the regulation of glucose homeostasis through the hepatic vagal efferents and insulin action on hepatic glucose production.

scholarly journals Combined deletion of free fatty-acid receptors 1 and 4 minimally impacts glucose homeostasis in mice

2020 ◽  
Author(s):  
Marine L. Croze ◽  
Arthur Guillaume ◽  
Mélanie Ethier ◽  
Grace Fergusson ◽  
Caroline Tremblay ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Dependent Manner ◽  
High Fat ◽  
Normal Chow ◽  
Free Fatty Acid Receptors

ABSTRACTThe free fatty-acid receptors FFAR1 (GPR40) and FFAR4 (GPR120) are implicated in the regulation of insulin secretion and insulin sensitivity, respectively. Although GPR120 and GPR40 share similar ligands, few studies have addressed possible interactions between these two receptors in the control of glucose homeostasis. Here we generated mice deficient in gpr120 (Gpr120KO) or gpr40 (Gpr40KO), alone or in combination (Gpr120/40KO), and metabolically phenotyped male and female mice fed a normal chow or high-fat diet. We assessed insulin secretion in isolated mouse islets exposed to selective GPR120 and GPR40 agonists singly or in combination. Following normal chow feeding, body weight and energy intake were unaffected by deletion of either receptor, although fat mass increased in Gpr120KO females. Fasting blood glucose levels were mildly increased in Gpr120/40KO mice, and in a sex-dependent manner in Gpr120KO and Gpr40KO animals. Oral glucose tolerance was slightly reduced in male Gpr120/40KO mice and in Gpr120KO females, whereas insulin secretion and insulin sensitivity were unaffected. In hyperglycemic clamps, the glucose infusion rate was lower in male Gpr120/40KO mice but insulin and c-peptide levels were unaffected. No changes in glucose tolerance were observed in either single or double KO animals under high-fat feeding. In isolated islets from wild-type mice, the combination of selective GPR120 and GPR40 agonists additively increased insulin secretion. We conclude that while simultaneous activation of GPR120 and GPR40 enhances insulin secretion ex vivo, combined deletion of these two receptors only minimally affects glucose homeostasis in vivo in mice.

scholarly journals Glucagon regulates hepatic mitochondrial function and biogenesis through FOXO1

2019 ◽  
Vol 241 (3) ◽  
pp. 265-278
Author(s):  
Wanbao Yang ◽  
Hui Yan ◽  
Quan Pan ◽  
James Zheng Shen ◽  
Fenghua Zhou ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Mitochondrial Function ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Complex Iii ◽  
Dependent Manner ◽  
Hepatic Glucose ◽  
Patients With Diabetes ◽  
High Level

Glucagon promotes hepatic glucose production maintaining glucose homeostasis in the fasting state. Glucagon maintains at high level in both diabetic animals and human, contributing to hyperglycemia. Mitochondria, a major place for glucose oxidation, are dysfunctional in diabetic condition. However, whether hepatic mitochondrial function can be affected by glucagon remains unknown. Recently, we reported that FOXO1 is an important mediator in glucagon signaling in control of glucose homeostasis. In this study, we further assessed the role of FOXO1 in the action of glucagon in the regulation of hepatic mitochondrial function. We found that glucagon decreased the heme production in a FOXO1-dependent manner, suppressed heme-dependent complex III (UQCRC1) and complex IV (MT-CO1) and inhibited hepatic mitochondrial function. However, the suppression of mitochondrial function by glucagon was largely rescued by deleting the Foxo1 gene in hepatocytes. Glucagon tends to reduce hepatic mitochondrial biogenesis by attenuating the expression of NRF1, TFAM and MFN2, which is mediated by FOXO1. In db/db mice, we found that hepatic mitochondrial function was suppressed and expression levels of UQCRC1, MT-CO1, NRF1 and TFAM were downregulated in the liver. These findings suggest that hepatic mitochondrial function can be impaired when hyperglucagonemia occurs in the patients with diabetes mellitus, resulting in organ failure.

Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women

2013 ◽  
Vol 38 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Marie-Soleil Beaudoin ◽  
Brian Allen ◽  
Gillian Mazzetti ◽  
Peter J. Sullivan ◽  
Terry E. Graham
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Insulin Response ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Dependent Manner ◽  
Caffeine Ingestion ◽  
Men And Women ◽  
C Peptide ◽  
Dose Dependent

The effects of alkaloid caffeine on insulin sensitivity have been investigated primarily in men, and with a single caffeine dose most commonly of 5–6 mg·kg−1 of body weight (BW). It is unknown if the effects of caffeine on glucose homeostasis are sex-specific and (or) dose-dependent. This study examined whether caffeine ingestion would disrupt glucose homeostasis in a dose-dependent or threshold manner. It also examined whether sex-specific responses to caffeine exist. It was hypothesized that women would have an exaggerated response to caffeine, and that caffeine would only impair glucose metabolism once a threshold was reached. Twenty-four healthy volunteers (12 males, 12 females) participated in 4 trials, in a crossover, randomized, and double-blind fashion. They ingested caffeine (1, 3, or 5 mg·kg−1 of BW) or placebo followed, 1 h later, by a 2-h oral glucose tolerance test. Glucose, insulin, C-peptide area under the curve (AUC), and insulin sensitivity index data were fitted to a segmented linear model to determine dose–responses. There were no differences between sexes for any endpoints. Regression slopes were significantly different from zero (p < 0.05) for glucose, insulin, and C-peptide AUCs, with thresholds being no different from zero. Increasing caffeine consumption by 1 mg·kg−1 of BW increased insulin and C-peptide AUCs by 5.8% and 8.7%, respectively. Despite this exaggerated insulin response, glucose AUC increased by 11.2 mmol per 120 min·L–1 for each mg·kg−1 BW consumed. These results showed that caffeine ingestion disrupted insulin sensitivity in a dose-dependent fashion beginning at very low doses (0–1 mg·kg−1 BW) in both healthy men and women.

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance

2010 ◽  
Vol 298 (1) ◽  
pp. E28-E37 ◽  
Author(s):  
Rajesh H. Amin ◽  
Suresh T. Mathews ◽  
Heidi S. Camp ◽  
Liyun Ding ◽  
Todd Leff
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Transgenic Mice ◽  
Muscle Tissue ◽  
Glucose Homeostasis ◽  
Muscle Cells ◽  
Whole Body ◽  
Fiber Types ◽  
Dependent Manner

The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ plays a key role in regulating whole body glucose homeostasis and insulin sensitivity. Although it is expressed most highly in adipose, it is also present at lower levels in many tissues, including skeletal muscle. The role muscle PPARγ plays in metabolic regulation and in mediating the antidiabetic effects of the thiazolidinediones is not understood. The goal of this work was to examine the molecular and physiological effects of PPARγ activation in muscle cells. We found that pharmacological activation of PPARγ in primary cultured myocytes, and genetic activation of muscle PPARγ in muscle tissue of transgenic mice, induced the production of adiponectin directly from muscle cells. This muscle-produced adiponectin was functional and capable of stimulating adiponectin signaling in myocytes. In addition, elevated skeletal muscle PPARγ activity in transgenic mice provided a significant protection from high-fat diet-induced insulin resistance and associated changes in muscle phenotype, including reduced myocyte lipid content and an increase in the proportion of oxidative muscle fiber types. Our findings demonstrate that PPARγ activation in skeletal muscle can have a significant protective effect on whole body glucose homeostasis and insulin resistance and that myocytes can produce and secrete functional adiponectin in a PPARγ-dependent manner. We propose that activation of PPARγ in myocytes induces a local production of adiponectin that acts on muscle tissue to improve insulin sensitivity.

scholarly journals Combined deletion of free fatty-acid receptors 1 and 4 minimally impacts glucose homeostasis in mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Marine L Croze ◽  
Arthur Guillaume ◽  
Mélanie Ethier ◽  
Grace Fergusson ◽  
Caroline Tremblay ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Dependent Manner ◽  
High Fat ◽  
Normal Chow ◽  
Free Fatty Acid Receptors

Abstract The free fatty-acid receptors FFAR1 (GPR40) and FFAR4 (GPR120) are implicated in the regulation of insulin secretion and insulin sensitivity, respectively. Although GPR120 and GPR40 share similar ligands, few studies have addressed possible interactions between these two receptors in the control of glucose homeostasis. Here we generated mice deficient in gpr120 (Gpr120KO) or gpr40 (Gpr40KO), alone or in combination (Gpr120/40KO), and metabolically phenotyped male and female mice fed a normal chow or high-fat diet. We assessed insulin secretion in isolated mouse islets exposed to selective GPR120 and GPR40 agonists singly or in combination. Following normal chow feeding, body weight and energy intake were unaffected by deletion of either receptor, although fat mass increased in Gpr120KO females. Fasting blood glucose levels were mildly increased in Gpr120/40KO mice, and in a sex-dependent manner in Gpr120KO and Gpr40KO animals. Oral glucose tolerance was slightly reduced in male Gpr120/40KO mice and in Gpr120KO females, whereas insulin secretion and insulin sensitivity were unaffected. In hyperglycemic clamps, the glucose infusion rate was lower in male Gpr120/40KO mice but insulin and c-peptide levels were unaffected. No changes in glucose tolerance were observed in either single or double KO animals under high-fat feeding. In isolated islets from wild-type mice, the combination of selective GPR120 and GPR40 agonists additively increased insulin secretion. We conclude that while simultaneous activation of GPR120 and GPR40 enhances insulin secretion ex vivo, combined deletion of these two receptors only minimally affects glucose homeostasis in vivo in mice.

Effects of stanniocalcin hormones on rat hepatic glucose homeostasis under fed and fasted conditions

2021 ◽  
Vol 302 ◽  
pp. 113661
Author(s):  
Samir Khal De Souza ◽  
Elaine Sarapio ◽  
Everton Lopes Vogt ◽  
Vanessa Schein ◽  
Rafael Bandeira Fabres ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Hepatic Glucose
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