Mechanisms of impaired insulin secretion after chronic excess of parathyroid hormone
| Autor: | Alessandra F. Perna, Xin-Jin Zhou, George Z. Fadda, Shaul G. Massry |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
endocrine system
medicine.medical_specialty Time Factors Physiology Phosphofructokinase-1 Glucose uptake medicine.medical_treatment Parathyroid hormone Deoxyglucose Biology Islets of Langerhans Adenosine Triphosphate Internal medicine Insulin Secretion medicine Animals Insulin Pancreatic hormone geography geography.geographical_feature_category Pancreatic islets Rats Inbred Strains Islet Rats Insulin oscillation Glucose Endocrinology medicine.anatomical_structure Parathyroid Hormone Secretagogue |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.1990.259.2.f210 |
| Popis: | Excess parathyroid hormone (PTH) in presence or absence of chronic renal failure impairs insulin release from pancreatic islets. This abnormality has been attributed to PTH-induced accumulation of Ca in the cytosol of the islets. Direct evidence for the latter phenomenon is lacking. This study examined the effect of chronic administration of PTH to rats with normal renal function on resting cytosolic Ca of the islets and evaluated the mechanisms through which a rise in resting cytosolic Ca may inhibit insulin secretion. After 42 days of PTH administration, glucose-induced insulin secretion was impaired, and this defect was corrected by the use of D-glyceraldehyde as secretagogue for insulin. Resting cytosolic Ca of islets from PTH-treated rats was markedly increased compared with that of islets from normal animals (288 +/- 27.1 vs. 135 +/- 3.7 nM, P less than 0.01), and their content of ATP in the presence of both 2.8 and 16.7 mM D-glucose was reduced (2.8 mM D-glucose, 4.6 +/- 0.17 vs. 6.0 +/- 0.42 pmol/islet, P less than 0.01; and 16.7 mM D-glucose, 6.9 +/- 0.25 vs. 11.1 +/- 0.95 pmol/islet, P less than 0.01). D-Glyceraldehyde increased ATP content in islets of PTH-treated rats from 4.6 +/- 0.17 to 8.8 +/- 0.71 pmol/islet. Glucose uptake by the islets, their insulin content, and both the Vmax and the apparent Km for fructose 6-phosphate of phosphofructokinase 1 (EC 2.7.1.11) in PTH-treated rats were not different from normal. The two major cellular derangements in the islets of PTH-treated rats were a reduction in ATP content and a rise in resting cytosolic Ca.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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