Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats.
Insulin sensitivity of skeletal muscle was studied in male offspring of rat dams fed either a 20% (control) or 8% (low-protein) diet during pregnancy and lactation. Freshly isolated muscle strips took up more [3H]methylglucose from low-protein animals than from controls (19.2 +/- 2.5 and 4.26 +/- 0.45 nmol.min-1.mg muscle-1, respectively, P < 0.001). However, after a 60-min preincubation there was no significant difference in basal glucose transport (4.02 +/- 0.42 and 4.23 +/- 0.35 nmol.min-1.mg-1 for control and low-protein animals, respectively). Insulin (300 pM) had a significantly greater (P < 0.001) effect on stimulation of glucose transport into preincubated low-protein muscle strips than into controls (to 14.14 +/- 1.25 and 9.61 +/- 0.71 nmol.min-1.mg-1, respectively). There were no differences in total GLUT-4 protein content. However, subcellular fractionation revealed significantly (P < 0.001) more GLUT-4 in muscle plasma membranes of low-protein animals compared with controls. Insulin increased (P < 0.001) the GLUT-4 content of control plasma membranes but had no effect in low-protein animals. There were twofold more insulin receptors in low-protein muscle membranes compared with controls (2.35 +/- 0.17 x 10(11) and 1.28 +/- 0.10 x 10(11) and insulin receptors/mg muscle membrane protein, respectively, P < 0.01). These results suggest that programming of muscle insulin sensitivity can occur during fetal life.
Ozanne
S E
SE
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, United Kingdom.
Wang
C L
CL
Coleman
N
N
Smith
G D
GD
D000818:Animals; D000831:Animals, Newborn; D018753:Diet, Protein-Restricted; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011247:Pregnancy; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007004:Hypoglycemic Agents; D007328:Insulin; D011506:Proteins