Insulin secretion defects in liver cirrhosis can be reversed by glucagon-like peptide-1.
Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release from isolated pancreatic islets of rats with CCl(4)-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzymes and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon concentrations were significantly greater (P<0.01) in cirrhotic rats than in control animals. Glucose (16.7 mM)-induced stimulation of insulin release from pancreatic islets revealed a twofold increase in control and cirrhotic rats. Basal and stimulated insulin secretion, however, were significantly lower in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GLP-1), has therapeutic potential for the treatment of type 2 diabetes. Therefore, islets from control and cirrhotic animals were incubated with GLP-1 in concentrations from 10(-)(11) to 10(-)(6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in patients with liver cirrhosis.
Siegel
E G
EG
Laboratory of Molecular Gastroenterology and Hepatology, Gastrointestinal Unit, 1st Department of Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
Seidenstücker
A
A
Gallwitz
B
B
Schmitz
F
F
Reinecke-Lüthge
A
A
Klöppel
G
G
Fölsch
U R
UR
Schmidt
W E
WE
D000704:Analysis of Variance; D000818:Animals; D002251:Carbon Tetrachloride; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D010634:Phenobarbital; D011498:Protein Precursors / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002251:Carbon Tetrachloride; D010634:Phenobarbital