Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy.
We investigated the functional impact of a recently described islet-specific loss of sympathetic nerves that occurs soon after the autoimmune destruction of beta-cells in the BB diabetic rat (35). We found that the portal venous (PV) glucagon response to sympathetic nerve stimulation (SNS) was markedly impaired in newly diabetic BB rats (BB D). We next found a normal glucagon response to intravenous epinephrine in BB D, eliminating the possibility of a generalized secretory defect of the BB D alpha-cell as the mediator of the impaired glucagon response to SNS. We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed. We therefore reproduced, in nondiabetic Wistar rats, an islet nerve terminal loss similar to that in BB D with systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. The impairment of the glucagon response to SNS in these chemically denervated, nondiabetic rats was similar to that in the spontaneously denervated BB D. We conclude that the early sympathetic islet neuropathy of BB D causes a functional defect of the sympathetic pathway to the alpha-cell that can, by itself, account for the impaired glucagon response to postganglionic SNS.
Mundinger
Thomas O
TO
Division of Endocrinology and Metabolism, Veterans Affairs Puget Sound Health Care System, and Department of Medicine, University of Washington, Seattle, USA. mundin@u.washington.edu
Mei
Qi
Q
Figlewicz
Dianne P
DP
Lernmark
Ake
A
Taborsky
Gerald J
GJ
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004558:Electric Stimulation; D004837:Epinephrine / Q000008:administration & dosage; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D007515:Islets of Langerhans / Q000737:chemistry / Q000294:innervation* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000032:analysis; D016627:Oxidopamine / Q000008:administration & dosage; D011169:Portal Vein; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D050492:Vesicular Biogenic Amine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D050492:Vesicular Biogenic Amine Transport Proteins; D016627:Oxidopamine; D005934:Glucagon; D004837:Epinephrine