[en] OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH METHODS AND PROCEDURES: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion. RESULTS: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-(2)H(2)-glucose) and total glucose output (measured with 2-(2)H(1)-glucose) were approximately 30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia. DISCUSSION: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Dirlewanger, Mirjam
Lefebvre, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Tappy, Luc
Language :
English
Title :
Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients.
Publication date :
2002
Journal title :
Obesity Research
ISSN :
1071-7323
eISSN :
1550-8528
Publisher :
North American Association for the Study of Obesity (NAASO), Silver Spring, United States - Maryland
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Ferrannini E, Locatelli L, Jéquier E, Felber J. Differential effects of insulin and hyperglycemia on intracellular glucose disposition in humans. Metabolism. 1989;38:459-65.
Ferrannini E, Groop LC. Hepatic glucose production in insulin-resistant states. Diabetes Metab Rev. 1989;5:711-25.
Lefèbvre P, Paolisso G, Scheen A. The role of glucagon in non-insulin-dependent (type 2) diabetes mellitus. In: Sakamoto N, Angel A, Hotta N, eds. New Directions in Research and Clinical Works for Obesity and Diabetes Mellitus. Amsterdam, The Netherlands: Elsevier Science Publishers BV; 1991, pp. 25-9.
DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM: a balanced overview. Diabetes Care. 1992;15: 318-68.
Felber JP, Acheson KJ, Tappy L. From Obesity to Diabetes. Chichester, UK: John Wiley & Sons; 1992.
Wajngot A, Chandramouli V, Schumann WC. Testing of the assumptions made in estimating futile cycling. Am J Physiol. 1989;256:E668-E75.
Finegood DT, Bergman RN, Vranic M. Estimation of endogenous glucose production during hyperinsulinemic euglycemic glucose clamps: comparison of labeled and unlabelled glucose infusates. Diabetes. 1987;36:914-24.
Wajngot A, Khan A, Giacca A, Vranic M, Efendic S. Dexamethasone increases glucose cycling, but not glucose production in healthy subjects. Am J Physiol. 1990;259: E626-E32.
Stumvoll M, Meyer C, Mitrakou A, Nadkarni V, Gerich JE. Renal glucose production and utilization: new aspects in humans. Diabetologia. 1997;40:749-57.
Robertson DA, Singh BM, Hale PJ, Nattrass M. Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion. Metab Clin Exp. 1992;41:604-12.
Escobar O, Mizuma H, Sothern MS, et al. Hepatic insulin clearance increases after weight loss in obese children and adolescents. Am J Med Sci. 1999;317:282-6.
DeFronzo RA. The triumvirate:β-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes. 1988;37:667-87.
Bergman RN, Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab. 2000;11: 351-6.
Vranic M. Banting lecture: glucose turnover: a key to understanding the pathogenesis of diabetes (indirect effects of insulin). Diabetes. 1992;41:1188-206.
Massillon D, Barzilai N, Hawkins M, Prus-Wertheimer D, Rossetti L. Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes. 1997;46:153-7.
Mevorach M, Giacca A, Aharon Y, Hawkins M, Shamoon H, Rossetti L. Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus. J Clin Invest. 1998;102:744-53.
Fery F. Role of hepatic glucose production and glucose up-take in the pathogenesis of fasting hyperglycemia in type 2 diabetes: normalization of glucose. J Clin Endocrinol Metab. 1994;78:536-42.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.