Effects of the somatostatin analog, octreotide, on glucose metabolism and insulin sensitivity in insulin-dependent diabetes mellitus.
To examine the effect of the somatostatin analog, octreotide, on insulin-mediated glucose uptake, seven insulin-dependent diabetic (IDDM) subjects were studied with and without 4 days of continuous subcutaneous octreotide administration (1 mg/kg/d). Insulin dosage was adjusted after frequent measurements of plasma glucose level. On the third day a hormonal and metabolic blood profile was obtained, and on the fourth day a euglycemic (5 mmol/L), hyperinsulinemic (1 mU/kg/min) clamp was performed in combination with calorimetry and a muscle biopsy. Mean plasma glucose levels on day 3 were similar (7.9 +/- 0.9 v 9.0 +/- 0.6 mmol/L). Growth hormone (GH) (0.39 +/- 0.10 v 0.78 +/- 0.23 mg/L, P < .05), insulin-like growth factor-1 (IGF-1) (127 +/- 17 v 157 +/- 21 mg/L, P < .05), and nonesterified fatty acids (NEFA) (239 +/- 25 v 405 +/- 44 mmol/L, P < .01) were lower following octreotide administration. Insulin requirements were reduced during octreotide administration, resulting in significantly lower insulin levels (27.3 +/- 2.7 v 39.9 +/- 9.9 mU/L, P < .5). During the clamp, glucose and insulin levels wer similar. Following octreotide, glucose disposal (7.33 +/- 0.49 v 6.08 +/- 0.55 mg/kg/min, P < .05) increased and hepatic glucose production (HGP) was more suppressed (-1.56 +/- 0.07 v -0.63 +/- 0.34 mg/kg/min, P < .05, 220 to 270 minutes). Oxidative glucose disposal (indirect calorimetry) was enhanced (3.09 +/- 0.24 v 2.70 +/- 0.37 mg/kg/min, P = .08), whereas glucose storage, as well as the fractional velocity for glycogen synthase activity, were unaltered during octreotide administration. Conversely, octreotide decreased lipid oxidation (0.12 +/- 0.1 v 0.41 +/- 0.15 mg/kg/min, P < .05). In conclusion, a low-dose octrotide infusion for 4 days to IDDM subjects leads to significantly increased insulin sensitivity.
Orskov
L
L
Department of Medicine C (Diabetes and Endocrinology), Arhus Amtssygehus, Arhus University Hospital, Denmark.
Møller
N
N
Bak
J F
JF
Pørksen
N
N
Schmitz
O
O
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006728:Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D015282:Octreotide / Q000008:administration & dosage* / Q000494:pharmacology
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D006006:Glycogen Synthase; D015282:Octreotide