title: Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses.
abstract: Short-term hyperglycemia suppresses superior cervical ganglia neurotransmission. If this ganglionic dysfunction also occurs in the islet sympathetic pathway, sympathetically mediated glucagon responses could be impaired. Our objectives were 1) to test for a suppressive effect of 7 days of streptozotocin (STZ) diabetes on celiac ganglia (CG) activation and on neurotransmitter and glucagon responses to preganglionic nerve stimulation, 2) to isolate the defect in the islet sympathetic pathway to the CG itself, and 3) to test for a protective effect of the WLD(S) mutation. We injected saline or nicotine in nondiabetic and STZ-diabetic rats and measured fos mRNA levels in whole CG. We electrically stimulated the preganglionic or postganglionic nerve trunk of the CG in nondiabetic and STZ-diabetic rats and measured portal venous norepinephrine and glucagon responses. We repeated the nicotine and preganglionic nerve stimulation studies in nondiabetic and STZ-diabetic WLD(S) rats. In STZ-diabetic rats, the CG fos response to nicotine was suppressed, and the norepinephrine and glucagon responses to preganglionic nerve stimulation were impaired. In contrast, the norepinephrine and glucagon responses to postganglionic nerve stimulation were normal. The CG fos response to nicotine, and the norepinephrine and glucagon responses to preganglionic nerve stimulation, were normal in STZ-diabetic WLD(S) rats. In conclusion, short-term hyperglycemia's suppressive effect on nicotinic acetylcholine receptors of the CG impairs sympathetically mediated glucagon responses. WLD(S) rats are protected from this dysfunction. The implication is that this CG dysfunction may contribute to the impaired glucagon response to insulin-induced hypoglycemia seen early in type 1 diabetes.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington; mundin@u.washington.edu.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Mundinger
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, Canada;
authors.forename: Ellis
authors.initials: E
authors.lastname: Cooper
authors.affiliation: The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, United Kingdom; and.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Coleman
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington; Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Taborsky
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015536:Down-Regulation / Q000187:drug effects; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005731:Ganglionic Stimulants / Q000494:pharmacology; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D006943:Hyperglycemia / Q000209:etiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D050505:Mutant Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014855:Wallerian Degeneration / Q000150:complications
chemical_list: D005731:Ganglionic Stimulants; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic; C533642:Wld protein, rat; D005934:Glucagon; D009638:Norepinephrine
keywords: WLDS; celiac ganglia; fos; glucagon; nicotinic acetylcholine receptors; norepinephrine; sympathetic nervous system