Differential effects of diabetes on adipocyte and liver phosphotyrosine and phosphoserine phosphatase activities.
We examined the activities of particulate and cytosolic phosphotyrosine phosphatase (PTPase) and phosphoserine phosphatase (PSPase) in adipocytes and livers of diabetic rats. PTPase activity was assessed with [32P]tyrosine-phosphorylated insulin receptor (IR), whereas PSPase activity was assayed with [32P]serine-phosphorylated glycogen synthase. Diabetes increased adipocyte particulate PTPase activity and enhanced IR dephosphorylation by 75% on the 2nd, 93% on the 14th, and 108% on the 30th day. In contrast, cytosolic PTPase activity decreased by 78% on the 14th and 45% on the 30th day (no change on the 2nd day). Similar changes were observed with PSPase (increased activity in particulate and decreased in cytosolic). Insulin therapy for 14 or 30 days restored PTPase and PSPase activities in both fractions. Vanadate, despite rapid normalization of glycemia, restored these activities only after 30 days of therapy. Diabetes-related changes in liver PTPase activity were observed on the 14th day only. At this time, it was increased in both particulate and cytosolic fractions. There was spontaneous normalization of the liver PTPase activity at 30 days of diabetes. In contrast, liver cytosolic PSPase activity was significantly inhibited and not normalized by the 30th day of disease without therapy. In summary, diabetes appears to induce tissue-specific changes in PTPase and PSPase activities resulting in significant alterations in dephosphorylation of IR and glycogen synthase. Moreover, there appears to be a differential regulation of PTPase and PSPase activities in diabetes, particularly in the liver.
Begum
N
N
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado.
Sussman
K E
KE
Draznin
B
B
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D046911:Macromolecular Substances; D008297:Male; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D012016:Reference Values; D014638:Vanadates / Q000494:pharmacology
D004988:Ethers, Cyclic; D007328:Insulin; D046911:Macromolecular Substances; D019319:Okadaic Acid; D014638:Vanadates; D006006:Glycogen Synthase; D011972:Receptor, Insulin; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase; D017027:Protein Tyrosine Phosphatases