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Bioactive GLP-1 in gut, receptor expression in pancreas, and insulin response to GLP-1 in diabetes-prone rats.
Endocrine 2004; 23(1):77-84E

Abstract

Glucagon-like peptide-1 (GLP-1) is the most insulinogenic of the glucagon-like peptides secreted mainly by L cells in the small and large intestine in response to the ingestion of nutrients. It binds to a specific GLP-1 receptor (GLP-1R) on beta-cells and can increase islet neogenesis and beta-cell mass. It is not clear whether the transmission of information from the gut to islet beta-cells by messengers such as GLP-1 is different in individuals who develop autoimmune diabetes. In the present study the expression of bioactive GLP-1 protein in the gut and its receptor in the pancreas was examined in diabetes-prone BioBreeding (BBdp) rats in the period before overt diabetes and in age-matched control, non-diabetes-prone BB (BBc) rats. An N-terminal directed antibody specific for the bioactive forms of GLP-1 (GLP-1(7-37) and GLP-1(7-36amide)) was used to mea-sure GLP-1 by radioimmunoassay in proximal, median, and distal gut. Pancreas GLP-1R area fraction, GLP-1R gene expression, and insulin content were analyzed, as were plasma GLP-1, glucose, and insulin. The concentration of GLP-1 protein in the jejunum and ileum of BBdp rats was lower than in BBc rats. Although these animals maintained normal blood glucose, there was impaired pancreatic endocrine function, characterized by low baseline insulin concentration in plasma and pancreas. GLP-1R mRNA expression was threefold less in islets isolated from BBdp rats, and GLP-1R+ islet area fraction in pancreas sections was decreased. When injected iv with GLP-1, BBdp rats displayed lower second-phase insulin response (and insulin/glucose ratios) compared with BBc rats. Thus, young BBdp rats displayed decreased concentrations of bioactive GLP-1 in jejunum and ileum, reduced GLP-1R in islets, and lower second-phase insulin response to iv GLP-1 than controls. The decrease in insulinogenic and islet beta-cell mass-promoting signal from GLP-1 in BBdp rats may contribute to impaired glucoregulation and ineffective maintenance of normal islet mass that shifts islet homeostasis in favor of development of diabetes.

Authors+Show Affiliations

Fundación Jiménez Díaz, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15034199

Citation

Valverde, Isabel, et al. "Bioactive GLP-1 in Gut, Receptor Expression in Pancreas, and Insulin Response to GLP-1 in Diabetes-prone Rats." Endocrine, vol. 23, no. 1, 2004, pp. 77-84.
Valverde I, Wang GS, Burghardt K, et al. Bioactive GLP-1 in gut, receptor expression in pancreas, and insulin response to GLP-1 in diabetes-prone rats. Endocrine. 2004;23(1):77-84.
Valverde, I., Wang, G. S., Burghardt, K., Kauri, L. M., Redondo, A., Acitores, A., ... Scott, F. W. (2004). Bioactive GLP-1 in gut, receptor expression in pancreas, and insulin response to GLP-1 in diabetes-prone rats. Endocrine, 23(1), pp. 77-84.
Valverde I, et al. Bioactive GLP-1 in Gut, Receptor Expression in Pancreas, and Insulin Response to GLP-1 in Diabetes-prone Rats. Endocrine. 2004;23(1):77-84. PubMed PMID: 15034199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bioactive GLP-1 in gut, receptor expression in pancreas, and insulin response to GLP-1 in diabetes-prone rats. AU - Valverde,Isabel, AU - Wang,Gen-Sheng, AU - Burghardt,Karolina, AU - Kauri,Lisa M, AU - Redondo,Araceli, AU - Acitores,Alicia, AU - Villanueva-Peñacarrillo,Maria L, AU - Courtois,Philippe, AU - Sener,Abdullah, AU - Cancelas,Jesús, AU - Malaisse,Willy J, AU - Scott,Fraser W, PY - 2003/11/05/received PY - 2004/01/05/revised PY - 2004/01/15/accepted PY - 2004/3/23/pubmed PY - 2004/11/4/medline PY - 2004/3/23/entrez SP - 77 EP - 84 JF - Endocrine JO - Endocrine VL - 23 IS - 1 N2 - Glucagon-like peptide-1 (GLP-1) is the most insulinogenic of the glucagon-like peptides secreted mainly by L cells in the small and large intestine in response to the ingestion of nutrients. It binds to a specific GLP-1 receptor (GLP-1R) on beta-cells and can increase islet neogenesis and beta-cell mass. It is not clear whether the transmission of information from the gut to islet beta-cells by messengers such as GLP-1 is different in individuals who develop autoimmune diabetes. In the present study the expression of bioactive GLP-1 protein in the gut and its receptor in the pancreas was examined in diabetes-prone BioBreeding (BBdp) rats in the period before overt diabetes and in age-matched control, non-diabetes-prone BB (BBc) rats. An N-terminal directed antibody specific for the bioactive forms of GLP-1 (GLP-1(7-37) and GLP-1(7-36amide)) was used to mea-sure GLP-1 by radioimmunoassay in proximal, median, and distal gut. Pancreas GLP-1R area fraction, GLP-1R gene expression, and insulin content were analyzed, as were plasma GLP-1, glucose, and insulin. The concentration of GLP-1 protein in the jejunum and ileum of BBdp rats was lower than in BBc rats. Although these animals maintained normal blood glucose, there was impaired pancreatic endocrine function, characterized by low baseline insulin concentration in plasma and pancreas. GLP-1R mRNA expression was threefold less in islets isolated from BBdp rats, and GLP-1R+ islet area fraction in pancreas sections was decreased. When injected iv with GLP-1, BBdp rats displayed lower second-phase insulin response (and insulin/glucose ratios) compared with BBc rats. Thus, young BBdp rats displayed decreased concentrations of bioactive GLP-1 in jejunum and ileum, reduced GLP-1R in islets, and lower second-phase insulin response to iv GLP-1 than controls. The decrease in insulinogenic and islet beta-cell mass-promoting signal from GLP-1 in BBdp rats may contribute to impaired glucoregulation and ineffective maintenance of normal islet mass that shifts islet homeostasis in favor of development of diabetes. SN - 1355-008X UR - https://www.unboundmedicine.com/medline/citation/15034199/Bioactive_GLP_1_in_gut_receptor_expression_in_pancreas_and_insulin_response_to_GLP_1_in_diabetes_prone_rats_ L2 - https://dx.doi.org/10.1385/ENDO:23:1:77 DB - PRIME DP - Unbound Medicine ER -