High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice.

Mosser RE, Maulis MF, Moullé VS, Dunn JC, Carboneau BA, Arasi K, Pappan K, Poitout V, Gannon M
Am J Physiol Endocrinol Metab. 2015 308 (7): E573-82

PMID: 25628421 · PMCID: PMC4385873 · DOI:10.1152/ajpendo.00460.2014

Both short- (1 wk) and long-term (2-12 mo) high-fat diet (HFD) studies reveal enhanced β-cell mass due to increased β-cell proliferation. β-Cell proliferation following HFD has been postulated to occur in response to insulin resistance; however, whether HFD can induce β-cell proliferation independent of insulin resistance has been controversial. To examine the kinetics of HFD-induced β-cell proliferation and its correlation with insulin resistance, we placed 8-wk-old male C57Bl/6J mice on HFD for different lengths of time and assayed the following: glucose tolerance, insulin secretion in response to glucose, insulin tolerance, β-cell mass, and β-cell proliferation. We found that β-cell proliferation was significantly increased after only 3 days of HFD feeding, weeks before an increase in β-cell mass or peripheral insulin resistance was detected. These results were confirmed by hyperinsulinemic euglycemic clamps and measurements of α-hydroxybutyrate, a plasma biomarker of insulin resistance in humans. An increase in expression of key islet-proliferative genes was found in isolated islets from 1-wk HFD-fed mice compared with chow diet (CD)-fed mice. These data indicate that short-term HFD feeding enhances β-cell proliferation before insulin resistance becomes apparent.

MeSH Terms (13)

Animals Cell Proliferation Diet, High-Fat Dietary Fats Glucose Clamp Technique Glucose Intolerance Glucose Tolerance Test Insulin-Secreting Cells Insulin Resistance Male Mice Mice, Inbred C57BL Time Factors

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