Biomaterial Database

Abnormal leucine-induced insulin secretion in chronic renal failure. 1994

H Y Oh, and G Z Fadda, and M Smogorzewski, and H H Liou, and S G Massry

Division of Nephrology, University of Southern California, School of Medicine, Los Angeles 90033.

Chronic renal failure (CRF) is associated with a sundry of abnormalities in pancreatic islets including a rise in their cytosolic calcium, reduced ATP content, and impaired glucose-induced insulin secretion. The latter is also stimulated by amino acids (such as leucine), and the cellular processes involved in leucine-induced insulin secretion are different from those responsible for glucose-induced insulin release. The present study examined whether leucine-induced insulin secretion is also impaired in CRF and investigated the cellular derangements for such a potential abnormality. The results showed that leucine-induced insulin secretion is markedly reduced by islets from CRF animals, and this defect was prevented by parathyroidectomy (PTX) of the CRF animals or by their treatment with verapamil, an agent that blocks the action of parathyroid hormone (PTH) on the pancreatic islets. Both leucine uptake and alpha-ketoisocaproic acid-induced insulin secretion by islets from CRF rats are normal; however, both the activation of glutamate dehydrogenase (GLDH) by leucine or by 2-aminobicyclo-[2-2-1]-haptene and the utilization of alpha-ketoglutarate are impaired, and the maximal reaction rate (Vmax) of glutaminase is reduced. These derangements are corrected by PTX of CRF rats or by their treatment with verapamil. The data demonstrate that 1) CRF is associated with impaired leucine-induced insulin secretion, 2) this defect is due to the state of secondary hyperparathyroidism of CRF, and 3) the cellular derangements responsible for this defect involve abnormalities in the metabolism of leucine and derangements in the leucine-GLDH-alpha-ketoglutarate-glutaminase pathway of the islets.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515	Islets of Langerhans	Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D007651	Keto Acids	Carboxylic acids that contain a KETONE group.	Oxo Acids,Oxoacids,Acids, Keto,Acids, Oxo
D007676	Kidney Failure, Chronic	The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.	ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007930	Leucine	An essential branched-chain amino acid important for hemoglobin formation.	L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D009392	Nephrectomy	Excision of kidney.	Heminephrectomy,Heminephrectomies,Nephrectomies
D010281	Parathyroid Hormone	A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.	Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body