Progressive and concurrent deterioration of vagus-stimulated and hypoglycemia-induced glucagon secretion in streptozotocin-diabetic rats.
The effects of left cervical vagus nerve stimulation on glucagon secretion were studied in streptozotocin-diabetic and age-matched control adult male rats. At two-week intervals, after the induction of streptozotocin-diabetes, streptozotocin-diabetic and age-matched control rats were anesthetized with chloral hydrate (350 mg/kg, ip). Left cervical vagus nerves were electrically stimulated via a Grass stimulator with 5-volt monophasic pulses of 3 msec duration at a frequency of 20 Hz for 1, 2, and 4 min. Arginine-induced glucagon secretion was also determined. Vagus nerve-stimulated (2 and 4 min) glucagon secretion deteriorated as the duration of streptozotocin-diabetes increased. Glucagon secretion in response to vagus nerve stimulation was virtually absent by 12 weeks of streptozotocin-diabetes. However, arginine-induced glucagon secretion was unaffected. Subsequent experiments showed that the defect in glucagon secretion from vagal stimulation occurred concurrently with that seen from insulin-induced hypoglycemia. These results indicate that the impaired hypoglycemia-induced glucagon secretion in long-term streptozotocin-diabetic rats may be correlated with the deterioration of the parasympathetic nervous system transmission in streptozotocin-diabetes.
Hertelendy
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Division of Pharmacology and Medicinal Chemistry, College of Pharmacy, University of Cincinnati Medical Center, OH 45267-0004.
Patel
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Skau
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D005934:Glucagon / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000502:physiology*
D007328:Insulin; D005934:Glucagon; D001120:Arginine