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Phosphate depletion impairs leucine-induced insulin secretion
H Y Oh1, G Z Fadda, M Smogorzewski
1Division of Nephrology, University of Southern California, School of Medicine, Los Angeles.
Journal of the American Society of Nephrology : JASN
|November 1, 1994
Summary
Phosphate depletion impairs insulin secretion triggered by L-leucine in rats. This occurs due to reduced metabolism of key intermediates and impaired enzyme activity within pancreatic islets.
Area of Science:
- Endocrinology
- Metabolic Research
- Cell Biology
Background:
- Phosphate depletion (PD) causes pancreatic islet dysfunction, affecting calcium levels, ATP content, and ATPase activity.
- L-leucine stimulates insulin secretion via ATP generation through KIC metabolism and GLDH activation.
Purpose of the Study:
- To investigate if phosphate depletion impairs L-leucine-induced insulin secretion.
- To identify the cellular mechanisms underlying potential impairments in leucine-induced insulin secretion during PD.
Main Methods:
- Studied pancreatic islets from phosphate-depleted (PD) rats and pair-weighed normal controls.
- Assessed L-leucine and KIC-induced insulin secretion.
- Measured enzyme activities (branched-chain keto acid dehydrogenase, GLDH, glutaminase) and metabolite concentrations (alpha-ketoglutarate).
Main Results:
- Phosphate depletion impaired both L-leucine- and KIC-induced insulin secretion.
- Reduced activity of branched-chain keto acid dehydrogenase and impaired GLDH activation were observed in PD rat islets.
- Basal alpha-ketoglutarate levels were elevated, and glutaminase activity was reduced in PD rat islets.
Conclusions:
- Phosphate depletion significantly impairs L-leucine-induced insulin secretion.
- Cellular defects in KIC and glutamate metabolism contribute to impaired insulin secretion in phosphate-depleted rats.