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Titolo:
The entero-insular axis in type 2 diabetes - incretins as therapeutic agents
Autore:
Creutzfeldt, W;
Indirizzi:
Univ Gottingen, Dept Med, Gottingen, Germany Univ Gottingen Gottingen Germany ottingen, Dept Med, Gottingen, Germany
Titolo Testata:
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
, volume: 109, anno: 2001, supplemento:, 2
pagine: S288 - S303
SICI:
0947-7349(2001)109:<S288:TEAIT2>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUCAGON-LIKE PEPTIDE-1; GASTRIC-INHIBITORY POLYPEPTIDE; CHOLECYSTOKININ RECEPTOR ANTAGONIST; RAT PANCREATIC-ISLETS; 7-36 AMIDE; INSULINOTROPIC ACTION; GLUCOSE-TOLERANCE; PHYSIOLOGICAL CONCENTRATIONS; ENDOCRINE SECRETION; GLP-1 7-36-AMIDE;
Keywords:
enteroinsular axis; incretin effect; GIP; GLP-1 [7-36] amide; GLP-1 for treatment of diabetes mellitus; dipeptidylpeptidase IV inhibition;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
120
Recensione:
Indirizzi per estratti:
Indirizzo: Creutzfeldt, W Klinikum Univ Goettingen, Zentrum Innere Med, Robert Kock Str 40, D-37075 Gottingen, Germany Klinikum Univ Goettingen Robert Kock Str 40 Gottingen Germany D-37075
Citazione:
W. Creutzfeldt, "The entero-insular axis in type 2 diabetes - incretins as therapeutic agents", EXP CL E D, 109, 2001, pp. S288-S303

Abstract

The search for intestinal factors regulating the endocrine secretion of the pancreas started soon after the discovery of secretin, i.e. nearly 100 years ago. Insulinotropic factors of the gut released by nutrients and stimulating insulin secretion in physiological concentrations in the presence of elevated blood glucose levels have been named incretins. Of the known gut hormones only gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1 [7-36] amide) fulfill this definition, - The incretin effect (i.e. the ratio between the integrated insulin response to an oral glucose load and an isoglycaemic intravenous glucose infusion) is markedly diminished in patients with type 2 diabetes mellitus, while the plasma levels of GIP and GLP-1 and their responses to nutrients are in the normal range. Therefore, a reduced responsiveness of the islet B-cells to incretins has been postulated. This insensitivity of the diabetic B-cells towards incretins canbe overcome by supraphysiological (pharmacological) concentrations of [7-36], however not of GIP. Accordingly, fasting and postprandial glucose levels can be normalized in patients with type 2 diabetes by infusions of GLP-1 [7-36]. Further studies reviealed that this is partially due to the fact that GLP-1 [7-36] - in addition to its insulinotropic effect - also inhibits glucagon secretion and delays gastric emptying. These three antidiabetic effects qualify GLP-1 [7-36] as an interesting therapeutic tool, mainly for type 2 diabetes. However, because of its short plasma half life time naturalGLP-1 [7-36] is not suitable for subcutaneous application. At present methods are being developed to improve the pharmacokinetics of GLP-1 by inhibition of the cleaving enzyme dipeptidyl peptidase IV (DPP-IV) or by synthesisof DPP-IV resistant GLP-1 analogues, Also naturally occurring GLP-1 analogues (for instance exendin-4) with a much longer half life time than GLP-1 [7-36] are being tested. - Thus, after 100 years of speculations and experimentations, incretins and their analogues are emerging as new antidiabetic drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 17:05:45