1. Secretion of glucagon-like peptide-1 and reactive hypoglycemia after partial gastrectomy
J J Andreasen, C Orskov, J J Holst Digestion. 1994;55(4):221-8. doi: 10.1159/000201151.
Glucagon-like peptide-1 is a peptide hormone from the distal small intestine which stimulates insulin secretion and inhibits glucagon secretion and thereby lowers blood glucose. This hormone, therefore, could be involved in the pathogenesis of postprandial reactive hypoglycemia. We subjected 8 patients showing symptoms of early dumping after partial gastrectomy to an oral 100 g glucose load and measured blood glucose and plasma insulin, C-peptide, glucagon, enteroglucagon and GLP-1 concentrations for 3.5 h after ingestion. Ten matched controls were treated similarly. The patients had higher blood glucose concentrations for the initial 60 min, but lower values for the remaining test period with a nadir of 2.76 +/- 0.19 mmol/l at 146 +/- 17 min after glucose (controls: 3.36 +/- 0.21 mmol/l at 210 +/- 9 min). GLP-1 and enteroglucagon responses were grossly elevated in patients compared to controls and insulin and C-peptide levels were higher during the initial 60 min. Glucagon concentrations increased in patients and decreased in controls. When hypoglycemia occurred, GLP-1 levels were only moderately elevated and insulin and C-peptide levels were lower and glucagon levels higher in patients than in controls. Thus, mechanisms other than release of GLP-1 seem to be responsible for the observed changes in the concentrations of glucose and glucoregulatory hormones.
2. Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy
Diva D De León, Shaoping Deng, Reza Madani, Rexford S Ahima, Daniel J Drucker, Doris A Stoffers Diabetes. 2003 Feb;52(2):365-71. doi: 10.2337/diabetes.52.2.365.
A reduction in beta-cell mass is an important causative factor in type 1 and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand beta-cell mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx) model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in islet growth. We examined beta-cell mass regeneration after 70% Ppx in mice receiving the GLP-1 antagonist Ex9-39 and in GLP-1R(-/-) mice. In Ex9-39-treated sham-operated mice, persistent fasting hyperglycemia was observed, but beta-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, beta-cell mass recovery of Ppx mice was not impaired by Ex9-39. In contrast, GLP-1R(-/-) CD1 mice showed worse glucose intolerance after Ppx compared with wild-type CD1 Ppx mice, and this correlated with a significant defect in beta-cell mass regeneration. The recovery of beta-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of beta-cell mass. These studies point to a role for endogenous GLP-1 in beta-cell regeneration after Ppx in mice.
3. Generation and Partial Characterization of Rabbit Monoclonal Antibody to Amyloid-β Peptide 1-37 (Aβ37)
Pankaj D Mehta, et al. J Alzheimers Dis. 2017;57(1):135-145. doi: 10.3233/JAD-161207.
Secreted soluble amyloid-β 1-37 (Aβ37) peptide is one of the prominent Aβ forms next to Aβ40, and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF Aβ37 levels in combination with Aβ38, Aβ40, and Aβ42 to support the diagnosis of patients with probable Alzheimer's disease (AD), and the value of antibody to Aβ37 to facilitate drug discovery studies. However, the availability of reliable and specific monoclonal antibody to Aβ37 is very limited. Our aims were: 1) to generate and partially characterize rabbit monoclonal antibody (RabmAb) to Aβ37, and 2) to determine whether the antibody detects changes in Aβ37 levels produced by a γ-secretase modulator (GSM). Our generated RabmAb to Aβ37 was found to be specific to Aβ37, since it did not react with Aβ36, Aβ38, Aβ39, Aβ40, and Aβ42 in an ELISA or immunoblotting. The epitope of the antibody was contained in the seven C-terminal residues of Aβ37. The antibody was sensitive enough to measure CSF and plasma Aβ37 levels in ELISA. Immunohistological studies showed the presence of Aβ37-positive deposits in the brain of AD, and Down syndrome persons diagnosed with AD. Our studies also showed that the antibody detected Aβ37 increases in CSF and brains of rodents following treatment with a GSM. Thus, our antibody can be widely applied to AD research, and in a panel based approach it may have potential to support the diagnosis of probable AD, and in testing the effect of GSMs to target AD.
