scholarly journals Age-Dependent Changes in Glucose Homeostasis in Male Deiodinase Type 2 Knockout Zebrafish

Endocrinology ◽  
2019 ◽  
Vol 160 (11) ◽  
pp. 2759-2772
Author(s):  
Anne M Houbrechts ◽  
An Beckers ◽  
Pieter Vancamp ◽  
Jurgen Sergeys ◽  
Conny Gysemans ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Glycogen Synthase ◽  
Receptor Expression ◽  
Cell Numbers ◽  
Glucose Levels ◽  
Islet Size ◽  
Insulin Receptor Expression ◽  
Kinase Expression

Abstract Thyroid hormones (THs) are crucial regulators of glucose metabolism and insulin sensitivity. Moreover, inactivating mutations in type 2 deiodinase (DIO2), the major TH-activating enzyme, have been associated with type 2 diabetes mellitus in both humans and mice. We studied the link between Dio2 deficiency and glucose homeostasis in fasted males of two different Dio2 knockout (KO) zebrafish lines. Young adult Dio2KO zebrafish (6 to 9 months) were hyperglycemic. Both insulin and glucagon expression were increased, whereas β and α cell numbers in the main pancreatic islet were similar to those in wild-types. Insulin receptor expression in skeletal muscle was decreased at 6 months, accompanied by a strong downregulation of hexokinase and pyruvate kinase expression. Blood glucose levels in Dio2KO zebrafish, however, normalized around 1 year of age. Older mutants (18 to 24 months) were normoglycemic, and increased insulin and glucagon expression was accompanied by a prominent increase in pancreatic islet size and β and α cell numbers. Older Dio2KO zebrafish also showed strongly decreased expression of glucagon receptors in the gastrointestinal system as well as decreased expression of glucose transporters GLUT2 and GLUT12, glucose-6-phosphatase, and glycogen synthase 2. This study shows that Dio2KO zebrafish suffer from transient hyperglycemia, which is counteracted with increasing age by a prominent hyperplasia of the endocrine pancreas together with decreases in hepatic glucagon sensitivity and intestinal glucose uptake. Further research on the mechanisms allowing compensation in older Dio2KO zebrafish may help to identify new therapeutic targets for (TH deficiency–related) hyperglycemia.

scholarly journals Pericyte control of pancreatic islet blood flow impacts glucose homeostasis

2021 ◽  
Author(s):  
Alejandro Tamayo ◽  
Luciana Mateus Goncalves ◽  
Rayner Rodriguez-Diaz ◽  
Elizabeth Pereira ◽  
Melissa Canales ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Plasma Insulin ◽  
Hormone Secretion ◽  
Hormonal Responses ◽  
Glucose Levels ◽  
Islet Blood Flow ◽  
Islet Dysfunction

The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long thought to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes, suggesting local control of blood flow. Here we determined the contribution of islet pericytes to the regulation of islet blood flow, plasma insulin and glucagon levels, and glycemia. Selective optogenetic activation of pericytes in intraocular islet grafts contracted capillaries and diminished blood flow. In awake mice, acute clamping of islet blood flow by optogenetic or pharmacological activation of pericytes disrupted hormonal responses, glycemia, and glucose tolerance. Our findings indicate that pericytes mediate vascular responses in the islet that are required for adequate hormone secretion and glucose homeostasis. Vascular deficiencies commonly seen in the islets of people with type 2 diabetes may impair regulation of islet blood flow and thus precipitate islet dysfunction.

scholarly journals Insulin Receptor Expression and Activity in the Brains of Nondiabetic Sporadic Alzheimer’s Disease Cases

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lap Ho ◽  
Shrishailam Yemul ◽  
Lindsay Knable ◽  
Pavel Katsel ◽  
Rudy Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Receptor ◽  
Glycogen Synthase ◽  
Hippocampal Formation ◽  
Receptor Expression ◽  
Sporadic Alzheimer’S Disease ◽  
Study Support ◽  
Insulin Receptor Expression ◽  
Signaling Components

We investigated the contents of the insulin receptor-beta subunit (IRβ) and [Tyr1162/1163]-phosphorylated IRβas surrogate indices of total IR content and IR activation in postmortem hippocampal formation brain specimens from nondiabetic sporadic Alzheimer’s disease (AD) cases. We found no significant changes in the brain contents of total IRβor [Tyr1162/1163]-phosphorylated IRβ, suggesting normal IR content and activation in the brains of nondiabetic sporadic AD cases. Moreover, total IRβand [Tyr1162/1163]-phosphorylated IRβlevels in the hippocampal formation are not correlated with the severity of amyloid or tau-neuropathology. Exploring the regulation of glycogen synthase kinase 3 (GSK3) α/β, key IR-signaling components, we observed significantly lower levels of total GSK3 α/βin brain specimens from nondiabetic AD cases, suggesting that impaired IR signaling mechanisms might contribute to the onset and/or progression of AD dementia. Outcomes from our study support the development of insulin-sensitizing therapeutic strategies to stimulate downstream IR signaling in nondiabetic AD cases.

Type-2 diabetes, a co-morbidity in Covid-19: does insulin signaling matter?

2021 ◽  
Author(s):  
Devanshi Mishra ◽  
Chinmoy Sankar Dey
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Homeostasis ◽  
Cross Talk ◽  
Insulin Signaling ◽  
Clinical Studies ◽  
Scientific Community ◽  
Major Objective ◽  
Glucose Levels ◽  
Co Morbidity

Type-2 Diabetes is associated with one of the co-morbidities due to SARS-Coronavirus 2 (SARS-Cov2) infection. Clinical studies show out of control glucose levels in SARS-Cov2 infected patients with type-2 diabetes. There is no experimental evidence suggesting aberrant molecular pathway(s) that explains why SARS-Cov2 infected patients with type-2 diabetes have uncontrolled glucose homeostasis and are co-morbid. In this article, we have highlighted major proteins involved in SARS-Cov2 infection, like, ACE 2, proteases like, TMPRSS2, Furin and their connectivity to insulin signaling molecules like, PI3K, Akt, AMPK, MAPK, mTOR, those regulate glucose homeostasis and the possible outcome of that cross-talk. We also raised concerns about the effect of anti-SARS-Cov2 drugs on patients with type-2 diabetes with reference to insulin signaling and the outcome of their possible cross-talk. There are no studies to decipher the possibilities of these obvious cross-talks. The major objective of this article is to urge the scientific community to explore the possibility of determining whether derangement of insulin signaling could be one of the possible causes of the patients with type-2 diabetes being co-morbid due to SARS-Cov2 infection.

Ternary complex factor regulates pancreatic islet size and blood glucose homeostasis in transgenic mice

2020 ◽  
Vol 159 ◽  
pp. 104983
Author(s):  
Andrea Lesch ◽  
Tobias M. Backes ◽  
Daniel S. Langfermann ◽  
Oliver G. Rössler ◽  
Matthias W. Laschke ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Transgenic Mice ◽  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Ternary Complex ◽  
Islet Size ◽  
Blood Glucose Homeostasis ◽  
Ternary Complex Factor

scholarly journals Abnormal Glucose Homeostasis and Pancreatic Islet Function in Mice with Inactivation of the Fem1b Gene

2005 ◽  
Vol 25 (15) ◽  
pp. 6570-6577 ◽  
Author(s):  
Deyin Lu ◽  
Tereza Ventura-Holman ◽  
Jing Li ◽  
Robert W. McMurray ◽  
Jose S. Subauste ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Sex Determination ◽  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Islet Function ◽  
Β Cells

ABSTRACT Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively. Here, we have developed Fem1b knockout (Fem1b-KO) mice, with targeted inactivation of Fem1b, a homolog of the nematode fem-1 sex determination gene. We show that the Fem1b-KO mice display abnormal glucose tolerance and that this is due predominantly to defective glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion is also affected. The Fem1b gene is expressed in pancreatic islets, within both β cells and non-β cells, and is highly expressed in INS-1E cells, a pancreatic β-cell line. In conclusion, these data implicate Fem1b in pancreatic islet function and insulin secretion, strengthening evidence that a genetic pathway homologous to nematode sex determination may be involved in glucose homeostasis and suggesting novel genes and processes as potential candidates in the pathogenesis of diabetes mellitus.

Pituitary GLP-1 receptor expression in the pathophysiology of type 2 diabetes

2019 ◽  
Author(s):  
M Boss ◽  
L Deden ◽  
M Brom ◽  
S van Lith ◽  
M Gotthardt
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Expression
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