Effect of a 2-day very low-energy diet on skeletal muscle insulin sensitivity in obese type 2 diabetic patients on insulin therapy.
This study investigates the molecular mechanisms underlying the blood glucose-lowering effect of a 2-day very low-energy diet (VLED, 1883 kJ/d) in 12 obese (body mass index, 36.3 +/- 1.0 kg/m2 [mean +/- SEM]) type 2 diabetic (HbA(1C) 7.3% +/- 0.4%) patients simultaneously taken off all glucose-lowering therapy, including insulin. Endogenous glucose production (EGP) and glucose disposal ([6,6-2H2]-glucose) were measured before and after the VLED in basal and hyperinsulinemic (40 mU/m2 per minute) euglycemic conditions. Insulin signaling and expression of GLUT-4, FAT/CD36, and triglycerides were assessed in muscle biopsies, obtained before the clamp and after 30 minutes of hyperinsulinemia. Fasting plasma glucose decreased from 11.3 +/- 1.3 to 10.3 +/- 1.0 mmol/L because of a decreased basal EGP (14.2 +/- 1.0 to 11.9 +/- 0.7 micromol/kg per minute, P = .009). Insulin-stimulated glucose disposal did not change. No diet effect was found on the expression of the insulin receptor and insulin receptor substrate-1 or on phosphatidylinositol 3'-kinase activity, or on FAT/CD36 expression pattern, GLUT-4 translocation, or triglyceride distribution in either the basal or insulin-stimulated situation. Unexpectedly, basal PKB/Akt phosphorylation on T308 and S473 increased after the diet, at equal protein expression. In conclusion, a 2-day VLED lowers fasting plasma glucose via a decreased basal EGP without an effect on glucose disposal. Accordingly, no changes in activation of phosphatidylinositol 3'-kinase, triglyceride distribution, FAT/CD36 expression, and GLUT-4 translocation were found in skeletal muscle biopsies.
Jazet
Ingrid M
IM
Department of General Internal Medicine C-4-66, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. i.m.jazet@lumc.nl
Ouwens
D Margriet
DM
Schaart
Gert
G
Pijl
Hanno
H
Keizer
Hans
H
Maassen
J Antonie
JA
Meinders
A Edo
AE
D001786:Blood Glucose / Q000032:analysis; D018955:CD36 Antigens / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004038:Diet, Reducing; D002149:Energy Intake; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D001786:Blood Glucose; D018955:CD36 Antigens; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt