Decreased ATP-induced synthesis and Ca(2+)-stimulated degradation of polyphosphoinositides in pancreatic islets from neonatally streptozotocin-diabetic rats.
Phosphoinositide (PI) synthesis and hydrolysis were investigated in pancreatic islet homogenates from neonatal streptozotocin diabetic (n-STZ) and control rats. In the diabetics, ATP, in absence of Ca2+, failed to increase the amount of phosphatidylinositol 4-phosphate (PtdInsP) and phosphatidyl inositol 4, 5-bisphosphate (PtdInsP2) at variance with the pattern in controls. Also, the Ca(2+)-stimulated generation of inositol phosphates (InsP) was dramatically decreased, whether in the absence or presence of ATP. Moreover, phosphatidylinositol (PtdIns) kinase activity was reduced while PtdInsP kinase activity was not impaired. These data suggest that the suppressed formation of PtdInsP and subsequent PtdInsP2 synthesis, concomitantly with a decreased Ca(2+)-stimulated phospholipase C activity, may participate to the alteration of the PI pathway, the limitation of the InsP production, and finally the impairment of the insulin release in the n-STZ model of non-insulin-dependent diabetes.
Morin
L
L
Laboratoire de Physiopathologie de la Nutrition, URA CNRS 307, Université Paris, France.
Giroix
M H
MH
Portha
B
B
D019870:1-Phosphatidylinositol 4-Kinase; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012016:Reference Values
D001786:Blood Glucose; D007295:Inositol Phosphates; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D018048:Receptors, Purinergic P2; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; D002118:Calcium