Glucose Sensing in Pancreatic β-Cells

A Model for the Study of Other Glucose-Regulated Cells in Gut, Pancreas, and Hypothalamus

  1. Frans C. Schuit,
  2. Peter Huypens,
  3. Harry Heimberg and
  4. Daniel G. Pipeleers
  1. From the Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium.
  1. Address correspondence and reprint requests to Frans C. Schuit, MD, PhD, Diabetes Research Center, Vrije Universiteit Brussel. E-mail: fschuit{at}minf.vub.ac.be .

Abstract

Nutrient homeostasis is known to be regulated by pancreatic islet tissue. The function of islet β-cells is controlled by a glucose sensor that operates at physiological glucose concentrations and acts in synergy with signals that integrate messages originating from hypothalamic neurons and endocrine cells in gut and pancreas. Evidence exists that the extrapancreatic cells producing and secreting these (neuro)endocrine signals also exhibit a glucose sensor and an ability to integrate nutrient and (neuro)hormonal messages. Similarities in these cellular and molecular pathways provide a basis for a network of coordinated functions between distant cell groups, which is necessary for an appropriate control of nutrient homeostasis. The glucose sensor seems to be a fundamental component of these control mechanisms. Its molecular characterization is most advanced in pancreatic β-cells, with important roles for glucokinase and mitochondrial oxidative fluxes in the regulation of ATP-sensitive K+ channels. Other glucose-sensitive cells in the endocrine pancreas, hypothalamus, and gut were found to share some of these molecular characteristics. We propose that similar metabolic signaling pathways influence the function of pancreatic α-cells, hypothalamic neurons, and gastrointestinal endocrine and neural cells.

Footnotes

  • α-MSH, α-melanocyte—stimulating hormone; AgRP, Agouti-related protein; ARC, arcuate hypothalamic nucleus; CART, cocaine and amphetamine—regulated transcript; G6P, glucose-6 phosphate; GIP, glucose-dependent insulinotropic peptide; GK, glucokinase; GLP-1, glucagon-like peptide 1; GLP-1R, GLP-1 receptor; HK, hexokinase I, hexokinase II, or hexokinase III enzyme activity; KATP, ATP-sensitive potassium channel; LHA, lateral hypothalamic area; MC3-R, melanocortin-receptor type 3; MC4-R, melanocortin-receptor type 4; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; PACAP, pituitary adenylate cyclase activating polypeptide; POMC, pro-opiomelanocortin; PVN, paraventricular nucleus; RT-PCR, reverse transcriptase—polymerase chain reaction; SUR1, sulfonylurea receptor 1; VIP, vasoactive intestinal polypeptide; VMH, ventromedial hypothalamus; VMN, ventromedial nucleus.

    • Accepted September 18, 2000.
    • Received February 8, 2000.
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