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

RE Mosser, MF Maulis, VS Moullé… - American Journal …, 2015 - journals.physiology.org
RE Mosser, MF Maulis, VS Moullé, JC Dunn, BA Carboneau, K Arasi, K Pappan, V Poitout
American Journal of Physiology-Endocrinology and Metabolism, 2015journals.physiology.org
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 …
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.
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