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22 December 2006

High fat diet modulation of glucose sensing in the beta-cell

Marlon E. Cerf

Med Sci Monit 2007; 13(1): RA12-17 :: ID: 470156

Abstract

Type 2 diabetes is primarily associated with beta-cell failure, insulin resistance and elevated hepatic glucose production. The islet beta-cell is specialized for the synthesis, storage and secretion of insulin. Beta-cell failure is characterized by the inability of the beta-cell to secrete suffi cient insulin in response to glucose, which ultimately results in hyperglycemia- the clinical hallmark of Type 2 diabetes. Impairment in glucose sensing contributes to beta-cell dysfunction. The facilitative glucose transporter, GLUT-2, and glucose phosphorylating enzyme, glucokinase, are key for glucose
sensing of the pancreatic beta-cell, the initial event in the pathway for glucose-stimulated insulin secretion. There is an increase in dietary fat intake, particularly saturated fat, in both the developing and Westernized world, which predisposes individuals to become obese and to potentially
develop insulin resistance, beta-cell dysfunction and Type 2 diabetes. A high fat diet is known to reduce both GLUT-2 and glucokinase expression thereby impairing glucose-stimulated insulin secretion. Furthermore, a high fat diet and specifi c free fatty acids, induces oxidative stress and apoptosis which reduces beta-cell mass and compromises beta-cell function. Glucose sensing is the initial event of glucose-stimulated insulin secretion therefore it is imperative to maintain adequate expression levels of GLUT-2 and GK for ensuring normal beta-cell function. The development of pharmaceutical agents that improve glucose-stimulated insulin secretion may replenish expression
of these glucose sensing genes after their attenuation by high fat feeding.

Keywords: Blood Glucose - metabolism, Dietary Fats - adverse effects, Insulin - secretion, Insulin-Secreting Cells - metabolism, Monosaccharide Transport Proteins - metabolism, Oxidative Stress - drug effects

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750