Functional levels of mitochondrial anion transport proteins in non-insulin-dependent diabetes mellitus.
The effect of non-insulin-dependent diabetes mellitus (i.e., NIDDM; type 2 diabetes) on the levels of functional mitochondrial anion transport proteins has been determined utilizing a chemically-induced neonatal model of NIDDM. We hypothesized that moderate insulin deficiency exacerbated by the insulin resistance, which is characteristic of NIDDM, would cause changes in mitochondrial anion transporter function that were similar to those we have previously shown to occur in insulin-dependent diabetes mellitus (i.e., IDDM; type 1 diabetes) (Arch. Biochem. Biophys. 280: 181-191, 1990). Our experimental approach consisted of the extraction of the pyruvate, dicarboxylate and citrate transport proteins from the mitochondrial inner membrane with Triton X-114 using rat liver mitoplasts (prepared from diabetic and control animals) as the starting material, followed by the functional reconstitution of each transporter in a proteoliposomal system. This strategy permitted the quantification of the functional levels of these three transporters in the absence of the complications that arise when such measurements are carried out with intact mitochondria (or mitoplasts). We found that experimental NIDDM did not cause significant changes in the extractable and reconstitutable specific (and total) transport activities of the pyruvate, dicarboxylate, and citrate transporters. These results are in marked contrast to our previous findings obtained using rats with IDDM and negated our hypothesis. The present results, in combination with our earlier findings, allow us to conclude that insulin plays an important role in the regulation of mitochondrial anion transporter function.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaplan
R S
RS
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile.
Mayor
J A
JA
Blackwell
R
R
Wilson
G L
GL
Schaffer
S W
SW
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D029382:Dicarboxylic Acid Transporters; D005947:Glucose; D008297:Male; D026901:Membrane Transport Proteins; D008930:Mitochondria, Liver / Q000378:metabolism*; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; D051381:Rats; D011919:Rats, Inbred Strains; D000070590:Solute Carrier Proteins; D013311:Streptozocin
D001786:Blood Glucose; D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; C000629174:Mpc1 protein, rat; D000070590:Solute Carrier Proteins; C020723:citrate-binding transport protein; D013311:Streptozocin; D005947:Glucose