AJP - Endocrinology and Metabolism, Vol 271, Issue 3 E587-E592, Copyright © 1996 by American Physiological Society

ARTICLES

Insulin resistance caused by hepatic cholinergic interruption and reversed by acetylcholine administration

H. Xie and W. W. Lautt
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

The role of hepatic parasympathetic nerves in insulin effectiveness was evaluated in fed anesthetized rats. Insulin sensitivity was assessed using a modified euglycemic clamp to quantitate the amount of glucose required to maintain euglycemia over 60 min after administration of insulin (50 mU/kg). With normal innervation, intraportal infusions of acetylcholine (ACh, 2.5 micrograms.kg-1.min-1) did not alter insulin sensitivity, but intraportal venous atropine (3 mg/kg) reduced insulin sensitivity (49.4 +/- 5.8%, P < 0.001, n = 7). Liver denervation resulted in reduction of insulin responsiveness by 70.8 +/- 5.8% (P < 0.001, n = 8), which was fully (96.8 +/- 12.5%) reversed by ACh. ACh into the portal vein reversed insulin resistance produced by denervation, but intravenous ACh was without effect, thus showing that the liver was the site of ACh action. Regression analysis suggests that some component of insulin response is not dependent on hepatic cholinergic nerve effects but that virtually all of the variability in response to insulin in normal fed rats tested under these conditions could be accounted for by variability in the hepatic parasympathetic-dependent insulin sensitivity. These data suggest a major role for hepatic parasympathetic nerves in regulation of whole body clearance of glucose in response to insulin.

This article has been cited by other articles:

				M. P. Guarino, N. C. Correia, W. W. Lautt, and M. P. Macedo Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G527 - G532. [Abstract] [Full Text] [PDF]

				M. C. Moore, S. Satake, B. Baranowski, P.-S. Hsieh, D. W. Neal, and A. D. Cherrington Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E286 - E296. [Abstract] [Full Text] [PDF]

				W. W. Lautt, M. P. Macedo, P. Sadri, S. Takayama, F. Duarte Ramos, and D. J. Legare Hepatic parasympathetic (HISS) control of insulin sensitivity determined by feeding and fasting Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G29 - G36. [Abstract] [Full Text] [PDF]

				M. C. Moore, P.-S. Hsieh, D. W. Neal, and A. D. Cherrington Nonhepatic response to portal glucose delivery in conscious dogs Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1271 - E1277. [Abstract] [Full Text] [PDF]

				P.-S. Hsieh, M. C. Moore, D. W. Neal, and A. D. Cherrington Importance of the hepatic arterial glucose level in generation of the portal signal in conscious dogs Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E284 - E292. [Abstract] [Full Text] [PDF]

				P.-S. Hsieh, M. C. Moore, B. Marshall, M. J. Pagliassotti, B. Shay, D. Szurkus, D. W. Neal, and A. D. Cherrington The head arterial glucose level is not the reference site for generation of the portal signal in conscious dogs Am J Physiol Endocrinol Metab, October 1, 1999; 277(4): E678 - E684. [Abstract] [Full Text] [PDF]

				P. Sadri and W. W. Lautt Blockade of hepatic nitric oxide synthase causes insulin resistance Am J Physiol Gastrointest Liver Physiol, July 1, 1999; 277(1): G101 - G108. [Abstract] [Full Text] [PDF]

				B. Ahren, P. Sauerberg, and C. Thomsen Increased insulin secretion and normalization of glucose tolerance by cholinergic agonism in high fat-fed mice Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E93 - E102. [Abstract] [Full Text] [PDF]

				P. Galassetti, C. A. Chu, D. W. Neal, G. W. Reed, D. H. Wasserman, and A. D. Cherrington A negative arterial-portal venous glucose gradient increases net hepatic glucose uptake in euglycemic dogs Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E126 - E134. [Abstract] [Full Text] [PDF]

				P.-S. Hsieh, M. C. Moore, D. W. Neal, M. Emshwiller, and A. D. Cherrington Rapid reversal of the effects of the portal signal under hyperinsulinemic conditions in the conscious dog Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E930 - E937. [Abstract] [Full Text] [PDF]