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Titolo:
ASPECTS OF NOVEL SITES OF REGULATION OF THE INSULIN STIMULUS-SECRETION COUPLING IN NORMAL AND DIABETIC PANCREATIC-ISLETS
Autore:
SJOHOLM A;
Indirizzi:
KAROLINSKA INST,KAROLINSKA HOSP,DEPT MOL MED,ROLF LUFT CTR DIABET RES,ENDOCRINE & DIABET UNIT S-17176 STOCKHOLM SWEDEN
Titolo Testata:
ENDOCRINE
fascicolo: 1, volume: 9, anno: 1998,
pagine: 1 - 13
SICI:
1355-008X(1998)9:1<1:AONSOR>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; BETA-CELL REPLICATION; GTP-BINDING PROTEINS; PYRUVATE-DEHYDROGENASE ACTIVITY; GLUCAGON-LIKE PEPTIDE-1; SENSITIVE K+ CHANNELS; FATTY-ACID OXIDATION; CHAIN ACYL-COA; ALPHA-ADRENERGIC INHIBITION; PHORBOL ESTER STIMULATION;
Keywords:
INSULIN SECRETION; PANCREATIC ISLET; DIABETES MELLITUS; PROTEIN PHOSPHATASE; CARNITINE PALMITOYLTRANSFERASE 1;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
224
Recensione:
Indirizzi per estratti:
Citazione:
A. Sjoholm, "ASPECTS OF NOVEL SITES OF REGULATION OF THE INSULIN STIMULUS-SECRETION COUPLING IN NORMAL AND DIABETIC PANCREATIC-ISLETS", ENDOCRINE, 9(1), 1998, pp. 1-13

Abstract

Noninsulin-dependent diabetes mellitus (NIDDM), a major health care problem in the Western world, is a disease typified by a relative deficiency of insulin, leading to vast derangements in glucose and lipid homeostasis with disastrous vascular complications. Despite immense research efforts aimed at a clear understanding of the etiology of this complex disease, the molecular mechanisms causing the disorder still remain elusive. This article reviews extant data from recent publicationsimplicating novel signal transduction pathways as important regulators of the insulin stimulus-secretion coupling in the pancreatic beta-cell. The significance of nitric oxide and serine/threonine protein phosphatases, and their inactivation by insulin secretagogues, glucose metabolites, ATP, GTP, glutamate, and inositol hexaphosphate in this arena is scrutinized. Additionally, also presented is the growing concept that an important signal for insulin secretion may reside in the inextricable interplay between glucose and lipid metabolism, specifically the generation of malonyl-CoA, which inhibits carnitine palmitoyltransferase 1 with the attendant accumulation of long-chain acyl CoA esters. Moreover, attention is directed towards novel intracellular actions of hypoglycemic sulfonylureas in the beta-cell. Finally, the importanceof ''lipotoxicity'' and aberrations in glucose uptake and metabolism in beta-cell dysfunction is given consideration. Future research efforts should aim at further characterization of effects of second messengers on protein phosphorylation elements in beta-cells. Additionally, long-term regulation by glucose and the diabetic state (e.g., fatty acids and ketones) on beta-cell protein phosphatases, pyruvate dehydrogenase, and carnitine palmitoyltransferase 1 needs to be explored in greater depth. Clearly, the detrimental impact of diabetic hyperlipidemia on beta-cell function has been a relatively neglected area, but futurepharmacological approaches directed at preventing lipotoxicity may prove beneficial in the treatment of diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 11:21:50