Aberrant insulin-induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother.
We examined the long-term effect of in utero exposure to streptozotocin-induced maternal diabetes on the progeny that postnatally received either ad libitum access to milk by being fed by control mothers (CM/DP) or were subjected to relative nutrient restriction by being fed by diabetic mothers (DM/DP) compared with the control progeny fed by control mothers (CM/CP). There was increased food intake, glucose intolerance, and obesity in the CM/DP group and diminished food intake, glucose tolerance, and postnatal growth restriction in the DM/DP group, persisting in the adult. These changes were associated with aberrations in hormonal and metabolic profiles and alterations in hypothalamic neuropeptide Y concentrations. By use of subfractionation and Western blot analysis techniques, the CM/DP group demonstrated a higher skeletal muscle sarcolemma-associated (days 1 and 60) and white adipose tissue plasma membrane-associated (day 60) GLUT4 in the basal state with a lack of insulin-induced translocation. The DM/DP group demonstrated a partial amelioration of this change observed in the CM/DP group. We conclude that the offspring of a diabetic mother with ad libitum postnatal nutrition demonstrates increased food intake and resistance to insulin-induced translocation of GLUT4 in skeletal muscle and white adipose tissue. This in turn leads to glucose intolerance and obesity at a later stage (day 180). Postnatal nutrient restriction results in reversal of this adult phenotype, thereby explaining the phenotypic heterogeneity that exists in this population.
Thamotharan
M
M
Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1752, USA.
McKnight
Robert A
RA
Thamotharan
Shanthie
S
Kao
Doris J
DJ
Devaskar
Sherin U
SU
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001692:Biological Transport; D003921:Diabetes Mellitus, Experimental; D004326:Drinking; D005260:Female; D005544:Forecasting; D018149:Glucose Intolerance / Q000209:etiology*; D051275:Glucose Transporter Type 4; D006130:Growth Disorders / Q000209:etiology; D007328:Insulin / Q000378:metabolism*; D007774:Lactation; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat