Regulation of glucose transport and expression of GLUT3 transporters in human circulating mononuclear cells: studies in cells from insulin-dependent diabetic and nondiabetic individuals.
We have previously shown that human circulating mononuclear cells (CMCs) respond to physiological concentrations of insulin with a rapid increase in glucose transport rate. The responding cells were found to be the monocytes, and cells derived from individuals with insulin-dependent diabetes mellitus (IDDM) had lower basal and insulin-stimulated glucose transport rates. Of interest, both cell types were found to express the GLUT1 but not the typical insulin-responsive GLUT4 transporter isoform. To further study the mechanisms responsible for stimulation of transport in these cells, we investigated (1) the response to insulin-like growth factor-I (IGF-I) and insulin-mimetic agents, and (2) the expression of other glucose transporter isoforms in CMCs of nondiabetic and IDDM individuals. The time course of insulin-stimulated glucose uptake in CMCs was rapid, reaching a plateau within 30 minutes. CMCs showed a dose-dependent and highly sensitive increase in glucose uptake to IGF-I (maximal response reached at 0.1 to 0.5 nmol/L IGF-I). The IGF-I dose-response curve was similar for CMCs of control and IDDM individuals, but both the basal and maximal response to IGF-I were lower in the diabetic group (P < .01). CMCs did not respond to vanadate, lithium, hydrogen peroxide, or short incubation (1 hour) with metformin, but glucose uptake increased in response to peroxides of vanadate and longer-duration (14 hours) metformin incubations. The glucose transporter isoforms of separated monocytes and lymphocytes were further investigated by Northern blotting of total RNA with a GLUT3-specific cDNA probe and by Western blotting of total membranes using GLUT3-specific antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)
Estrada
D E
DE
Department of Pediatrics (Endocrine Division), Hospital for Sick Children, Toronto, Ontario, Canada.
Elliott
E
E
Zinman
B
B
Poon
I
I
Liu
Z
Z
Klip
A
A
Daneman
D
D
D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D015152:Blotting, Northern; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors
D051274:Glucose Transporter Type 3; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495687:SLC2A3 protein, human; D007334:Insulin-Like Growth Factor I; D008687:Metformin; D005947:Glucose