c-peptide and glucagon-like-peptide-1-(7-36)

The aim of this study was to determine whether rapid conversion to inactive and potentially antagonistic peptides could alter the response to GLP-1.. We evaluated the ability of exendin-4, a GLP-1 analogue resistant to degradation by dipeptidyl peptidase IV, to modulate insulin-induced stimulation of glucose uptake and suppression of glucose production in eight healthy subjects during infusion of GLP-1 (1.2 pmol.kg(-1).min(-1)), exendin-4 (0.12 pmol.kg(-1).min(-1)), or saline. Glucose was clamped at 5.3 mmol/l and insulin was infused to progressively increase insulin concentrations to about 65, 190 and 700 pmol/l, respectively. Endogenous insulin secretion was inhibited with somatostatin to ensure comparable portal insulin concentrations while glucagon and growth hormone were maintained at basal concentrations.. Glucose, insulin, C-peptide, glucagon and growth hormone concentrations did not differ on the three occasions. In contrast, cortisol concentrations were greater during both exendin-4 (25.1+/-4.4 mmol/l per 7 h; p<0.01) and GLP-1, (17.0+/-2.0 mmol/l 7 h; p<0.05) than saline (13.5+/-1.5 mmol/l per 7 h). While insulin-induced stimulation of glucose disappearance at the highest insulin concentrations tended to be greater and insulin-induced suppression of glucose production lower in the presence of exendin-4 or GLP-1 than saline, the differences were not significant.. Exendin-4 and GLP-1 increase cortisol secretion in human subjects. However, neither alters insulin action in non-diabetic human subjects. These data also suggest that the lack of an effect of GLP-1 on insulin action is not likely to be explained by rapid degradation to inactive or antagonistic peptides.

Topics: Adult; Animals; Biotransformation; Blood Glucose; Body Mass Index; C-Peptide; Dipeptidyl Peptidase 4; Exenatide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Human Growth Hormone; Humans; Hydrocortisone; Infusions, Intravenous; Insulin; Kinetics; Lizards; Peptide Fragments; Peptides; Reference Values; Venoms

The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.

Topics: Adult; C-Peptide; Fasting; Food; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Secretion; Male; Peptide Fragments; Proinsulin

The biological effects and the metabolism of the intestinal hormone glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 were studied in normal healthy subjects. GLP-1 7-36 amide and GLP-1 7-37 equipotently stimulated insulin secretion (integrated hormone response 0-60 min, 631 +/- 211 vs. 483 +/- 177 pmol/h x L-1) and C-peptide secretion (integrated hormone response 9064 +/- 1804 vs. 9954 +/- 2031 pmol/h x L-1) and equipotently lowered plasma glucose (integrated decrease 48.3 +/- 5.7 vs. 46.2 +/- 8.4 mmol/h x L-1) and plasma glucagon (integrated decrease 80.4 +/- 24.3 vs. 156.0 +/- 34.6 pmol/h x L-1). Both GLP-1 7-36 amide and GLP-1 7-37 lowered the plasma concentration of free fatty acids significantly. The plasma half-lives of GLP-1 7-36 amide and GLP-1 7-37 were 5.3 +/- 0.4 vs. 6.1 +/- 0.8 min, and the metabolic clearance rates of the two peptides also were similar (14.6 +/- 2.4 vs. 12.2 +/- 1.0 pmol/kg x min). In conclusion, COOH-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Male; Peptide Fragments; Structure-Activity Relationship; Time Factors