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Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients.
J Hepatol. 1998 Feb; 28(2):280-91.JH

Abstract

BACKGROUND/AIMS

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+Show Affiliations

Kruszynska YT
Department of Endocrinology and Metabolism, VA Medical Center, University of California San Diego, La Jolla 92093, USA.
Goulas S
No affiliation info available
Wollen N
No affiliation info available
McIntyre N
No affiliation info available

MeSH

AdultAgedArginineBasal MetabolismBlood GlucoseC-PeptideCase-Control StudiesDiabetes ComplicationsDiabetes MellitusDose-Response Relationship, DrugGlucagonGlucoseHumansHyperglycemiaInsulinInsulin SecretionIslets of LangerhansLiver Cirrhosis, AlcoholicMiddle AgedSecretory Rate

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9514541

Citation

Kruszynska, Y T., et al. "Insulin Secretory Capacity and the Regulation of Glucagon Secretion in Diabetic and Non-diabetic Alcoholic Cirrhotic Patients." Journal of Hepatology, vol. 28, no. 2, 1998, pp. 280-91.
Kruszynska YT, Goulas S, Wollen N, et al. Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients. J Hepatol. 1998;28(2):280-91.
Kruszynska, Y. T., Goulas, S., Wollen, N., & McIntyre, N. (1998). Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients. Journal of Hepatology, 28(2), 280-91.
Kruszynska YT, et al. Insulin Secretory Capacity and the Regulation of Glucagon Secretion in Diabetic and Non-diabetic Alcoholic Cirrhotic Patients. J Hepatol. 1998;28(2):280-91. PubMed PMID: 9514541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients. AU - Kruszynska,Y T, AU - Goulas,S, AU - Wollen,N, AU - McIntyre,N, PY - 1998/3/26/pubmed PY - 1998/3/26/medline PY - 1998/3/26/entrez SP - 280 EP - 91 JF - Journal of hepatology JO - J Hepatol VL - 28 IS - 2 N2 - BACKGROUND/AIMS: 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. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/9514541/Insulin_secretory_capacity_and_the_regulation_of_glucagon_secretion_in_diabetic_and_non_diabetic_alcoholic_cirrhotic_patients_ DB - PRIME DP - Unbound Medicine ER -