Diabetes alters the responses of glucagon secreting cells and vascular bed to isoprenaline and forskolin in vitro in rat pancreas.
Diabetes is known to disturb pancreatic glucagon secreting alpha cell function and blood flow control. In a previous study we could show that streptozotocin-induced diabetes suppressed adenosine stimulating effect on glucagon secretion and reduced its vasodilatory properties; since the nucleotide exerts these effects by activation of A2 purinergic receptors known to be positively coupled to adenylate cyclase, we investigated the effect of streptozotocin diabetes on the responses of alpha cells and vascular bed to stimulation of adenylate cyclase through 2 different ways: 1) with isoprenaline by activation of beta adrenergic receptor positively coupled to the enzyme; 2) with forskolin by direct activation of the catalytic unit of adenylate cyclase. In the isolated perfused pancreas of normal rats, isoprenaline (0.01 microM) or forskolin (1 microM) induced a +200 to +300% increase of glucagon secretion and a 20 to 30% increase of pancreatic vascular flow rate. In pancreas of 5-week diabetic rats, alpha cell responses to isoprenaline and forskolin were completely suppressed and the vasodilatory effects of both drugs were significantly reduced (-35 to -50%). Long term in vivo insulin treatment with glycaemia normalization was able to correct both defects. We can conclude that streptozotocin diabetes suppresses glucagon secretion and reduces pancreatic vasodilatation not only in response to activation of receptors positively coupled to adenylate cyclase but also to a direct activation of this enzyme.
Gross
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R
Faculté de Médecine, Laboratoire de Pharmacologie, CNRS URA 599, Montpellier, France.
Hillaire-Buys
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Ribes
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Loubatières-Mariani
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MM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D005576:Colforsin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D005934:Glucagon; D000262:Adenylyl Cyclases; D007545:Isoproterenol