Diabetes Drug Reduces Insulin Secretion of β-CellsLast Updated: May 11, 2009. The antidiabetic drug pioglitazone may preserve pancreatic β-cell function by reducing insulin secretion at intermediate glucose concentrations and reducing the energy metabolism of the cells, according to a study published online April 30 in Endocrinology.
MONDAY, May 11 (HealthDay News) -- The antidiabetic drug pioglitazone may preserve pancreatic β-cell function by reducing insulin secretion at intermediate glucose concentrations and reducing the energy metabolism of the cells, according to a study published online April 30 in Endocrinology.
Julien Lamontagne, from the Universite de Montreal in Canada, and colleagues treated pancreatic β-cells and rat islets with pioglitazone for periods of up to 90 minutes to examine the effect of the drug on glucose-induced insulin secretion, activation of AMP-activated protein kinase (AMPK, a key regulator of energy metabolism), and β-cell metabolism.
The researchers found that pioglitazone treatment led to a reduction in insulin secretion at intermediate glucose concentrations only, by shifting the dose-dependence curve of glucose responsiveness to the right. The effect of pioglitazone on insulin secretion could be reversed by an AMPK inhibitor. The antidiabetic agents metformin and berberine, which also activate AMPK, similarly caused a right shift in the dose dependence of glucose-induced insulin secretion. Pioglitazone was associated with changes in energy metabolism, including reduced glucose oxidation, mitochondrial membrane polarization, adenosine triphosphate levels, palmitate esterification into complex lipids, and lipolysis.
"In conclusion, pioglitazone acutely reduces glucose oxidation, energy metabolism and glycerolipid/fatty acid cycling of the β-cell at intermediate glucose concentrations," Lamontagne and colleagues write. "We suggest that AMPK activation and the metabolic 'deceleration' of the β-cell caused by pioglitazone contribute to its known effects to reduce hyperinsulinemia and preserve β-cell function, and to act as an antidiabetic agent."
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