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Attenuation of diabetic kidney injury in DPP4-deficient rats; role of GLP-1 on the suppression of AGE formation by inducing glyoxalase 1.
Abstract Dipeptidyl peptidase 4 (DPP4) inactivates incretin hormone glucagon-like peptide-1. DPP4 inhibitors may exert beneficial effects on diabetic nephropathy (DN) independently of glycemic control; however, the mechanisms underlying are not fully understood. Here, we investigated the mechanisms of the beneficial effects of DPP4 inhibition on DN using DPP4-deficient (DPP4-def) rats and rat mesangial cells.Blood glucose and HbA1c significantly increased by streptozotocin (STZ) and no differences were between WT-STZ and DPP4-def-STZ. The albumin level in urine decreased significantly and the albumin/creatinine ra...
Source: Aging - January 5, 2020 Category: Biomedical Science Authors: Sarker MK, Lee JH, Lee DH, Chun KH, Jun HS Tags: Aging (Albany NY) Source Type: research

The core clock gene, Bmal1, and its downstream target, the SNARE regulatory protein secretagogin, are necessary for circadian secretion of glucagon-like peptide-1
ConclusionsThese data demonstrate, for the first time, that mice display a circadian pattern in GLP-1 secretion, which is impaired in Bmal1 knockout mice, and that Bmal1 regulation of Scgn expression plays an essential role in the circadian release of the incretin hormone, GLP-1.
Source: Molecular Metabolism - November 21, 2019 Category: Endocrinology Source Type: research

Intestinal CART is a regulator of GIP and GLP-1 secretion and expression
Publication date: Available online 6 April 2018Source: Molecular and Cellular EndocrinologyAuthor(s): L. Shcherbina, A. Lindqvist, A.-H. Thorén Fischer, E. Ahlqvist, E. Zhang, S.E. Falkmer, E. Renström, J. Koffert, H. Honka, N. WierupAbstractImpaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression.CART expression was foun...
Source: Molecular and Cellular Endocrinology - July 10, 2018 Category: Endocrinology Source Type: research

Alpha7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of Enteroendocrine L Cells In Vitro.
Abstract Enteroendocrine L cells secrete the incretin hormone glucagon-like peptide-1 (GLP-1) and they also express the α7 nicotinic acetylcholine receptor (α7nAChR) that might regulate GLP-1 secretion. Here, GTS-21, a selective α7nAChR agonist, was used to examine the impact of α7nAChR activation in L-cell lines, mouse intestinal primary cell cultures, and C57BL/6 mice. GTS-21 stimulated GLP-1 secretion in vitro and this effect was attenuated by an α7nAChR antagonist or by α7nAChR-specific siRNA. Under in vitro cell culture conditions of glucotoxicity, GTS-21 restored GLP-1 secretion and improved L-cell via...
Source: Endocrinology - July 9, 2018 Category: Endocrinology Authors: Wang D, Meng Q, Leech CA, Yepuri N, Zhang L, Holz GG, Wang C, Cooney RN Tags: Endocrinology Source Type: research

Intestinal CART is a regulator of GIP and GLP-1 secretion and expression
Publication date: Available online 6 April 2018Source: Molecular and Cellular EndocrinologyAuthor(s): L. Shcherbina, A. Lindqvist, A.-H. Thorén Fischer, E. Ahlqvist, E. Zhang, S.E. Falkmer, E. Renström, J. Koffert, H. Honka, N. WierupAbstractImpaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression.CART expression was foun...
Source: Molecular and Cellular Endocrinology - July 5, 2018 Category: Endocrinology Source Type: research

Patients with Long QT Syndrome Due to Impaired hERG-encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia.
Conclusions -Besides a prolonged cardiac repolarization phase, LQT2 patients display increased GLP-1, GIP and insulin secretion and defective glucagon secretion causing decreased plasma glucose and thus increased risk of hypoglycemia. Furthermore, glucose ingestion increased QT interval and aggravated the cardiac repolarization disturbances in LQT2 patients. Clinical Trial Registration -ClinicalTrials.gov Identifier: NCT02775513. PMID: 28235848 [PubMed - as supplied by publisher]
Source: Circulation - February 23, 2017 Category: Cardiology Authors: Hyltén-Cavallius L, Iepsen EW, Wewer Albrechtsen NJ, Svendstrup M, Lubberding AF, Hartmann B, Jespersen T, Linneberg A, Christiansen M, Vestergaard H, Pedersen O, Holst JJ, Kanters JK, Hansen T, Torekov SS Tags: Circulation Source Type: research

A Critical Role for {beta}-Catenin in Modulating Levels of Insulin Secretion from {beta}-Cells by Regulating Actin Cytoskeleton and Insulin Vesicle Localization Cell Biology
In conclusion, we find that β-catenin levels modulate Ca2+-dependent insulin exocytosis under conditions of glucose, GLP-1, or KCl stimulation through a role in modulating insulin secretory vesicle localization and/or fusion via actin remodeling. These findings also provide insights as to how the overexpression of TCF7L2 may attenuate insulin secretion.
Source: Journal of Biological Chemistry - December 8, 2016 Category: Chemistry Authors: Brie Sorrenson, Emmanuelle Cognard, Kathryn L. Lee, Waruni C. Dissanayake, Yanyun Fu, Weiping Han, William E. Hughes, Peter R. Shepherd Tags: Molecular Bases of Disease Source Type: research

Altered expression of uncoupling protein 2 in GLP-1-producing cells after chronic high glucose exposure: implications for the pathogenesis of diabetes mellitus
Glucagon-like peptide-1 (GLP-1) is a gut L-cell hormone that enhances glucose-stimulated insulin secretion. Several approaches that prevent GLP-1 degradation or activate the GLP-1 receptor are being used to treat type 2 diabetes mellitus (T2DM) patients. In T2DM, GLP-1 secretion has been suggested to be impaired, and this defect appears to be a consequence rather than a cause of impaired glucose homeostasis. However, although defective GLP-1 secretion has been correlated with insulin resistance, little is known about the direct effects of chronic high glucose concentrations, which are typical in diabetes patients, on GLP-1...
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Urbano, F., Filippello, A., Di Pino, A., Barbagallo, D., Di Mauro, S., Pappalardo, A., Rabuazzo, A. M., Purrello, M., Purrello, F., Piro, S. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research

CEACAM2 in GLP-1 Secretion Metabolism
This study investigated whether CEACAM2 also regulates insulin secretion. Ceacam2 deletion caused an increase in β-cell secretory function, as assessed by hyperglycemic clamp analysis, without affecting insulin response. Although CEACAM2 is expressed in pancreatic islets predominantly in non-β-cells, basal plasma levels of insulin, glucagon and somatostatin, islet areas, and glucose-induced insulin secretion in pooled Cc2−/− islets were all normal. Consistent with immunofluorescence analysis showing CEACAM2 expression in distal intestinal villi, Cc2−/− mice exhibited a higher release of oral glucose-mediated GLP-...
Source: Journal of Biological Chemistry - January 8, 2016 Category: Chemistry Authors: Ghanem, S. S., Heinrich, G., Lester, S. G., Pfeiffer, V., Bhattacharya, S., Patel, P. R., DeAngelis, A. M., Dai, T., Ramakrishnan, S. K., Smiley, Z. N., Jung, D. Y., Lee, Y., Kitamura, T., Ergun, S., Kulkarni, R. N., Kim, J. K., Giovannucci, D. R., Najjar Tags: Metabolism Source Type: research

Altered Expression of Uncoupling Protein 2 in GLP-1-producing Cells after Chronic High Glucose Exposure: Implications for the Pathogenesis of Diabetes Mellitus.
Abstract Glucagon-like peptide-1 (GLP-1) is a gut L-cell hormone that enhances glucose-stimulated insulin secretion. Several approaches that prevent GLP-1 degradation or activate the GLP-1 receptor are being used to treat type 2 diabetes mellitus (T2DM) patients. In T2DM, GLP-1 secretion has been suggested to be impaired, and this defect appears to be a consequence rather than a cause of impaired glucose homeostasis. However, although defective GLP-1 secretion has been correlated with insulin resistance, little is known about the direct effects of chronic high glucose concentrations, which are typical in diabetes ...
Source: American Journal of Physiology. Cell Physiology - January 6, 2016 Category: Cytology Authors: Urbano F, Filippello A, Di Pino A, Barbagallo D, Di Mauro S, Pappalardo A, Rabuazzo AM, Purrello M, Purrello F, Piro S Tags: Am J Physiol Cell Physiol Source Type: research

Ghrelin regulates GLP-1 production through mTOR signaling in L cells
Publication date: 15 November 2015 Source:Molecular and Cellular Endocrinology, Volume 416 Author(s): Geyang Xu, Xiaosi Hong, Hong Tang, Sushi Jiang, Fenting Liu, Zhemin Shen, Ziru Li, Weizhen Zhang Glucagon-like peptide (GLP-1), an intestinal incretin produced in L-cells and released in response to meal intake, functions to promote insulin secretion and to decrease plasma glucose. Ghrelin is an orexigenic hormone critical for glucose homeostasis. The molecular mechanism by which ghrelin alters GLP-1 production remains largely unknown. Here we showed that ghrelin attenuates GLP-1 production through mTOR signaling...
Source: Molecular and Cellular Endocrinology - October 14, 2015 Category: Endocrinology Source Type: research