HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db06-1776v1 56/6/1703    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bock, G. Articles by Rizza, R. A. Search for Related Content PubMed PubMed Citation Articles by Bock, G. Articles by Rizza, R. A. Social Bookmarking                What's this?

Contribution of Hepatic and Extrahepatic Insulin Resistance to the Pathogenesis of Impaired Fasting Glucose

Role of Increased Rates of Gluconeogenesis

From the Division of Endocrinology, Diabetes, Metabolism & Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota

Address correspondence and reprint requests to Robert A. Rizza, MD, Mayo Clinic, 200 1st St. SW, Room 5-194 Joseph, Rochester, MN 55905. E-mail: rizza.robert{at}mayo.edu

Abbreviations: EGP, endogenous glucose production; FFA, free fatty acid; IFG, impaired fasting glucose; NFG, normal fasting glucose

OBJECTIVE—To determine the contribution of hepatic insulin resistance to the pathogenesis of impaired fasting glucose (IFG).

RESEARCH DESIGN AND METHODS—Endogenous glucose production (EGP) and glucose disposal were measured in 31 subjects with IFG and 28 subjects with normal fasting glucose (NFG) after an overnight fast and during a clamp when endogenous secretion was inhibited with somatostatin and insulin infused at rates that approximated portal insulin concentrations present in IFG subjects after an overnight fast (80 pmol/l, "preprandial") or within 30 min of eating (300 pmol/l, "prandial").

RESULTS—Despite higher (P < 0.001) insulin and C-peptide concentrations and visceral fat (P < 0.05), fasting EGP and glucose disposal did not differ between IFG and NFG subjects, implying hepatic and extrahepatic insulin resistance. This was confirmed during preprandial insulin infusion when glucose disposal was lower (P < 0.05) and EGP higher (P < 0.05) in IFG than in NFG subjects. Higher EGP was due to increased (P < 0.05) rates of gluconeogenesis in IFG. EGP was comparably suppressed in IFG and NFG groups during prandial insulin infusion, indicating that hepatic insulin resistance was mild. Glucose disposal remained lower (P < 0.01) in IFG than in NFG subjects.

CONCLUSIONS—Hepatic and extrahepatic insulin resistance contribute to fasting hyperglycemia in IFG with the former being due at least in part to impaired insulin-induced suppression of gluconeogenesis. However, since hepatic insulin resistance is mild and near-maximal suppression of EGP occurs at portal insulin concentrations typically present in IFG subjects within 30 min of eating, extrahepatic (but not hepatic) insulin resistance coupled with accompanying defects in insulin secretion is the primary cause of postprandial hyperglycemia.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?