Long-term normalization of GLUT-4 protein content in skeletal muscle of diabetic rats following islet transplantation.
Skeletal muscle GLUT-4 content is decreased in streptozotocin (STZ)-diabetic rats. This decrease is associated with impairment in glucose transport across the plasma membrane. In this study we investigated whether islet transplantation might normalize GLUT-4 content. Transplantation of syngeneic islets restored long-term near-normoglycemia in STZ-diabetic Lewis rats. Transplanted rats, followed up to 6 months, maintained slightly but significantly higher fasting and fed glucose levels when compared with age-matched normal controls. Although fasting insulin levels of transplanted rats were significantly higher than those of controls, insulin levels did not increase significantly with feeding. Plasma glucose levels following an oral glucose load (2 g/kg) were only slightly higher than in normal controls 2 months after transplantation, whereas after 6 months more severe glucose intolerance was detected. Transplanted rats completely lost the first-phase insulin release in response to i.v. glucose although they showed an increased second phase and preserved response to arginine. Six months after transplantation, endocrine beta cell mass of the grafts was similar to pretransplantation values. GLUT-4 protein content in skeletal muscle homogenates was reduced in untreated diabetic animals whereas it was completely restored by islet transplantation. In conclusion, achievement of long-term nearnormoglycemia after islet transplantation was associated with complete normalization of skeletal muscle GLUT-4 content in the diabetic animals, even in the presence of abnormal glucose tolerance and an altered pattern of insulin secretion.
Davalli
A M
AM
Department of Medicine, New England Deaconess Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Napoli
R
R
Weitgasser
R
R
Capotorto
J V
JV
Hirshman
M F
MF
Finegood
D T
DT
Bonner-Weir
S
S
Horton
E S
ES
Weir
G C
GC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000601:surgery; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat