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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells
Fei Li1, D Marshall Porterfield, Xi-Yan Zheng
1Department of General Surgery, Digestive Medical Center, the First Affiliated Hospital, Medical School, Tsinghua University, Beijing 100016, China.
Chinese Medical Journal
|April 12, 2012
Summary
Impaired mitochondrial function in diabetic pancreatic beta cells disrupts calcium (Ca2+) influx, leading to abnormal insulin secretion. This study clarifies the link between mitochondrial health and insulin release in type 2 diabetes.
Area of Science:
- Endocrinology
- Cell Biology
- Metabolic Diseases
Background:
- Type 2 diabetes is linked to abnormal insulin secretion from pancreatic beta cells.
- Impaired mitochondrial function and calcium (Ca2+) influx in beta cells are implicated in diabetes etiology.
- Understanding the interplay between mitochondrial function, Ca2+ influx, and insulin secretion is crucial.
Purpose of the Study:
- To investigate the detailed relationship between mitochondrial function, Ca2+ influx, and defective insulin secretion in pancreatic beta cells.
- To elucidate the mechanisms underlying impaired insulin secretion in type 2 diabetes.
Main Methods:
- Mitochondrial function and morphology were assessed in pancreatic beta cells of diabetic KK-Ay mice and control C57BL/6J mice.
- Whole-cell patch-clamp recording was used to evaluate L-type and store-operated Ca2+ (SOC) channel activities.
- Glucose-induced Ca2+ influx was measured using non-invasive micro-test (NMT) technology.
Main Results:
- Diabetic mice exhibited swollen mitochondria with disordered cristae and decreased mitochondrial function.
- Ca2+ channel activity was increased, and glucose-induced Ca2+ influx was impaired in diabetic beta cells.
- Genipin treatment could restore impaired glucose-induced Ca2+ influx.
Conclusions:
- Defective mitochondrial function in pancreatic beta cells is a primary cause of abnormal insulin secretion in type 2 diabetes.
- Altered Ca2+ influx, not Ca2+ channel activity, mediates the effect of mitochondrial dysfunction on insulin secretion.
- Targeting mitochondrial function may offer therapeutic strategies for type 2 diabetes.
