RT Journal Article
SR Electronic
T1 Brain Glucose Sensors Play a Significant Role in the Regulation of Pancreatic Glucose-Stimulated Insulin Secretion
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 321
OP 328
DO 10.2337/db11-1050
VO 61
IS 2
A1 Osundiji, Mayowa A.
A1 Lam, Daniel D.
A1 Shaw, Jill
A1 Yueh, Chen-Yu
A1 Markkula, S. Pauliina
A1 Hurst, Paul
A1 Colliva, Carolina
A1 Roda, Aldo
A1 Heisler, Lora K.
A1 Evans, Mark L.
YR 2012
UL http://diabetes.diabetesjournals.org/content/61/2/321.abstract
AB 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.