Mechanisms of hyperglycemia-induced insulin resistance in whole body and skeletal muscle of type I diabetic patients.

Abstract

To examine the mechanisms of hyperglycemia-induced insulin resistance, eight insulin-dependent (type I) diabetic men were studied twice, after 24 h of hyperglycemia (mean blood glucose 20.0 +/- 0.3 mM, i.v. glucose) and after 24 h of normoglycemia (7.1 +/- 0.4 mM, saline) while receiving identical diets and insulin doses. Whole-body and forearm glucose uptake were determined during a 300-min insulin infusion (serum free insulin 359 +/- 22 and 373 +/- 29 pM, after hyper- and normoglycemia, respectively). Muscle biopsies were taken before and at the end of the 300-min insulin infusion. Plasma glucose levels were maintained constant during the 300-min period by keeping glucose for 150 min at 16.7 +/- 0.1 mM after 24-h hyperglycemia and increasing it to 16.5 +/- 0.1 mM after normoglycemia and by allowing it thereafter to decrease in both studies to normoglycemia. During the normoglycemic period (240-300 min), total glucose uptake (25.0 +/- 2.8 vs. 33.8 +/- 3.9 mumol.kg-1 body wt.min-1, P less than 0.05) was 26% lower, forearm glucose uptake (11 +/- 4 vs. 18 +/- 3 mumol.kg-1 forearm.min-1, P less than 0.05) was 35% lower, and nonoxidative glucose disposal (8.9 +/- 2.2 vs. 19.4 +/- 3.3 mumol.kg-1 body wt-1min-1, P less than 0.01) was 54% lower after 24 h of hyper- and normoglycemia, respectively. Glucose oxidation rates were similar. Basal muscle glycogen content was similar after 24 h of hyperglycemia (234 +/- 23 mmol/kg dry muscle) and normoglycemia (238 +/- 22 mmol/kg dry muscle). Insulin increased muscle glycogen to 273 +/- 22 mmol/kg dry muscle after 24 h of hyperglycemia and to 296 +/- 33 mmol/kg dry muscle after normoglycemia (P less than 0.05 vs. 0 min for both). Muscle ATP, free glucose, glucose-6-phosphate, and fructose-6-phosphate concentrations were similar after both 24-h treatment periods and did not change in response to insulin. We conclude that a marked decrease in whole-body, muscle, and nonoxidative glucose disposal can be induced by hyperglycemia alone.

• Authors: H Vuorinen-Markkola, V A Koivisto, H Yki-Jarvinen
• Journal: Diabetes (Diabetes) Vol. 41 Issue 5 Pg. 571-80 (May 1992) ISSN: 0012-1797 [Print] United States
• PMID: 1568526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fatty Acids, Nonesterified
• Fructosephosphates
• Glucosephosphates
• Insulin
• Lactates
• Serum Albumin
• Glucose-6-Phosphate
• fructose-6-phosphate
• Adenosine Triphosphate
• Growth Hormone
• Glycogen
• Potassium
• Hydrocortisone

Topics

• Adenosine Triphosphate (analysis)
• Adult
• Biopsy
• Blood Glucose (analysis)
• Circadian Rhythm
• Diabetes Mellitus, Type 1 (blood, pathology, physiopathology)
• Energy Metabolism (physiology)
• Fatty Acids, Nonesterified (blood)
• Fructosephosphates (analysis)
• Glucose-6-Phosphate
• Glucosephosphates (analysis)
• Glycogen (analysis)
• Growth Hormone (blood)
• Humans
• Hydrocortisone (blood)
• Hyperglycemia (physiopathology)
• Insulin (blood)
• Insulin Resistance (physiology)
• Lactates (blood)
• Male
• Muscles (chemistry, pathology, physiopathology)
• Osmolar Concentration
• Oxidation-Reduction
• Potassium (blood)
• Serum Albumin (analysis)