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Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Osundiji, Mayowa A 
Lam, Daniel D 
Shaw, Jill 
Yueh, Chen-Yu 
Markkula, S Pauliina 

Abstract

As patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic β-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucokinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC0-10). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosamine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes.

Description

Keywords

Animals, Glucokinase, Glucose, Glucose Tolerance Test, Hypothalamus, Injections, Intraventricular, Insulin, Insulin Secretion, Male, Mannoheptulose, Pancreas, Rats, Rats, Sprague-Dawley

Journal Title

Diabetes

Conference Name

Journal ISSN

0012-1797
1939-327X

Volume Title

61

Publisher

American Diabetes Association
Sponsorship
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065171)
Medical Research Council (G0600717)
Juvenile Diabetes Research Foundation Ltd (JDRF) (1-2006-29)
Wellcome Trust (081713/Z/06/Z)
Juvenile Diabetes Research Foundation Ltd (JDRF) (1-2003-78)