Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats.
We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.1 mM) caused a distinct biphasic pattern of IRI release from the control pancreas, whereas the first phase was marginal and the second phase was absent in the diabetic pancreas. Arginine (20 mM)-induced IRI release was similar in both groups, whereas IRG release was greater in the control rats than in the diabetic rats. Thus, this model of STZ-D simulates a certain class of non-insulin-dependent diabetes mellitus (NIDDM). In these diabetic animals, the cholecystokinin (CCK) analogue ceruletide (620 pM) caused a significantly greater increase in IRI release in the presence of 5.6 mM glucose than in the control rats, but ceruletide caused a similar IRG release in both groups. Because CCK and ceruletide stimulate phosphoinositide turnover in pancreatic islets, we examined the effects of carbachol and phorbol ester TPA on IRI release in the presence of 5.6 mM glucose. Carbachol (10 microM), which is thought to generate similar second messengers as ceruletide, induced greater IRI release in diabetic than in control rats. TPA (100 nM) caused a significantly greater increase in IRI release from the diabetic than the control pancreas. Our results demonstrate that the insulin-releasing mechanism involved in protein kinase C activation is enhanced in this model of NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Okabayashi
Y
Y
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Otsuki
M
M
Ohki
A
A
Tani
S
S
Baba
S
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D013311:Streptozocin; D002108:Ceruletide; D002217:Carbachol; D005934:Glucagon; D001120:Arginine; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate