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Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets
Published on: May 11, 2015
Malic enzyme is present in mouse islets and modulates insulin secretion.
1Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA.
Diabetologia
|September 20, 2008
Summary
Mouse islets possess malic enzyme (ME), crucial for insulin secretion regulation. This finding contrasts previous reports and clarifies beta cell metabolic pathways in both rats and mice.
Area of Science:
- Metabolic regulation in pancreatic beta cells.
- Enzymology and molecular biology of glucose homeostasis.
Background:
- The pyruvate-malate shuttle is vital for pancreatic beta cell function, with cytosolic malic enzyme (ME) generating NADPH.
- ME's role in insulin secretion, obesity, and insulin resistance is established in rats, but its presence in mouse islets was uncertain.
- Previous studies suggested mouse islets lack ME activity, implying divergent insulin secretion mechanisms between rodents.
Purpose of the Study:
- To investigate the presence and function of malic enzyme (ME) in mouse pancreatic islets.
- To determine if ME activity in mouse islets is altered in obesity and insulin resistance models.
- To elucidate the role of ME in regulating insulin secretion and NADPH production in mouse beta cells.
Main Methods:
- Quantification of ME activity using fluorometric enzymatic assays and Me mRNA via real-time PCR in mouse islets.
- Analysis of ME activity in islets from streptozotocin-treated mice and FACS-purified beta cells.
- Assessment of insulin secretion and NADPH/NADP(+) ratios in beta cells following ME siRNA treatment.
Main Results:
- ME activity and Me mRNA were detected in C57BL/6 mouse islets, challenging prior assumptions.
- ME activity was reduced in streptozotocin-induced diabetes but significantly increased in obese agouti-L mouse islets and MIN-6 cells.
- ME inhibition via siRNA impaired glucose-stimulated insulin secretion and reduced NADPH production in beta cells.
Conclusions:
- Mouse islets express functional malic enzyme (ME).
- ME activity is implicated in regulating insulin secretion and NADPH homeostasis in mouse beta cells.
- This study resolves discrepancies regarding ME presence in mouse islets and highlights its conserved role in insulin secretion.
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