title: Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients.
abstract: OBJECTIVE
  Insulin secretion is increased in cirrhotic patients without diabetes but decreased in cirrhotic patients with diabetes. Increased glucagon secretion is found in both groups. Our aim was to determine: 1) whether alterations in insulin secretion are due to changes in maximal secretory capacity or altered islet B-cell sensitivity to glucose, and 2) whether regulation of glucagon secretion by glucose is disturbed.
  
  
  METHODS
  Insulin, C-peptide and glucagon levels were measured basally and during 12, 19 and 28 mmol/l glucose clamps, and in response to 5 g intravenous arginine basally and after 35 min at a glucose of 12, 19 and 28 mmol/l in 6 non-diabetic alcoholic cirrhotic patients, six diabetic alcoholic cirrhotic patients and six normal controls.
  
  
  RESULTS
  Fasting insulin, and C-peptide levels were higher in cirrhotic patients than controls but not different between diabetic and non-diabetic patients. C-peptide levels at t=35 min of the clamp increased more with glucose concentration in non-diabetic cirrhotic patients than controls; there was little increase in diabetic cirrhotic patients. At a blood glucose of approximately 5 mmol/l the 2-5 min C-peptide response to arginine (CP[ARG]) was similar in all groups, but enhancement of this response by glucose was greater in non-diabetic cirrhotic patients and impaired in diabetic cirrhotic patients. Maximal insulin secretion (CP(ARG) at 28 mmol/l glucose) was 49% higher in the non-diabetic cirrhotic patients than controls (p<0.05); in diabetic cirrhotic patients it was 47% lower (p<0.05). The glucose level required for half-maximal potentiation of (CPARG) was not different in the three groups. Cirrhotic patients had higher fasting glucagon levels, and a greater 2-5-min glucagon response to arginine, which was enhanced by concomitant diabetes (p<0.001 vs controls). Suppression of plasma glucagon by hyperglycaemia was markedly impaired in diabetic cirrhotic patients (glucagon levels at 35 min of 28 mmol/l glucose clamp: diabetics, 139 x/divided by 1.25 ng/l, non-diabetic cirrhotic patients, 24 x/divided by 1.20, controls, 21 x/divided by 1.15, p<0.001). Suppression of arginine-stimulated glucagon secretion by glucose was also impaired in diabetic cirrhotic patients, and to a lesser extent in non-diabetic cirrhotic patients.
  
  
  CONCLUSIONS
  Insulin secretory abnormalities in diabetic and non-diabetic cirrhotic patients are due to changes in maximal secretory capacity rather than altered B-cell sensitivity to glucose. The exaggerated glucagon response to arginine in alcoholic cirrhotic patients is not abolished by hyperglycaemia/hyperinsulinaemia. In diabetic alcoholic cirrhotic patients, the inhibitory effect of glucose on basal glucagon secretion is also markedly impaired.
authors.affiliation: Department of Endocrinology and Metabolism, VA Medical Center, University of California San Diego, La Jolla 92093, USA.
authors.forename: Y T
authors.initials: YT
authors.lastname: Kruszynska
authors.forename: S
authors.initials: S
authors.lastname: Goulas
authors.forename: N
authors.initials: N
authors.lastname: Wollen
authors.forename: N
authors.initials: N
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000494:pharmacology; D001481:Basal Metabolism; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D016022:Case-Control Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000503:physiopathology*; D008875:Middle Aged; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D005947:Glucose