glucagon-like-peptide-1-(7-36)amide and Chronic-Disease

The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20-120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m(2)); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1alpha gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All participants underwent three hyperglycemic clamps (2 h, 15 mM) with continuous infusion of saline, 1 pmol GLP-1 (7-36)amide/kg body weight.min or 4 pmol GIP pmol/kg body weight.min. The early-phase (0-20 min) plasma insulin response tended to be enhanced by both GIP and GLP-1, compared with glucose alone, in all five groups. In contrast, the late-phase (20-120 min) plasma insulin response to GIP was attenuated, compared with the plasma insulin response to GLP-1, in all five groups. Significantly higher glucose infusion rates were required during the late phase of the GLP-1 stimulation, compared with the GIP stimulation. In conclusion, lack of GIP amplification of the late-phase plasma insulin response to glucose seems to be a consequence of diabetes mellitus, characterizing most, if not all, forms of diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Male; Middle Aged; Neurotransmitter Agents; Nuclear Proteins; Pancreatitis; Peptide Fragments; Phenotype; Protein Precursors; Transcription Factors

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.

Topics: Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Pancreatitis; Peptide Fragments