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Essentiality of portal vein receptors in hypoglycemic counterregulation: direct proof via denervation in male canines.

Abstract：

:A major issue of in the treatment of diabetes is the risk of hypoglycemia. Hypoglycemia is detected both centrally and peripherally in the porto-hepatic area. The portal locus for hypoglycemic detection was originally described using the "local irrigation of the liver" approach in a canine model. Further work using portal vein denervation (DEN) in a rodent model characterized portal hypoglycemic sensing in detail. However, recent controversy about the relevance of rodent findings to large animals and humans prompted us to investigate the effect of portal DEN on the hypoglycemic response in the canine, a species with multiple similarities to human glucose homeostasis. Hypoglycemic hyperinsulinemic clamps were performed in male canines, before (PRE) and after (POST) portal vein DEN or sham surgery (CON, control). Insulin (30 pmol/kg·min) and glucose (variable) were infused to slowly decrease systemic glycemia to 50 mg/dL over 160 minutes. The average plasma glucose during clamp steady state was: 2.9 ± 0.1 mmol DEN-PRE, 2.9 ± 0.2 mmol DEN-POST, 2.9 ± 0.1 mmol CON-PRE, and 2.8 ± 0.0 mmol CON-POST. There were no significant differences in plasma insulin between DEN and CON, PRE and POST experiments. The epinephrine response to hypoglycemia was reduced by 62% in DEN but not in CON. Steady-state cortisol was 46% lower after DEN but not after CON. Our study shows, in a large animal model, that surgical disconnection of the portal vein from the afferent pathway of the hypoglycemic counterregulatory circuitry results in a substantial suppression of the epinephrine response and a significant impact on cortisol response. These findings directly demonstrate an essential role for the portal vein in sensing hypoglycemia and relating glycemic information to the central nervous system.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Ionut V,Castro AV,Woolcott OO,Stefanovski D,Iyer MS,Broussard JL,Mkrtchyan H,Burch M,Elazary R,Kirkman E,Bergman RN

doi

10.1210/en.2013-1794

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

1247-54

issue

eissn

0013-7227

issn

1945-7170

journal_volume

155

pub_type

杂志文章

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Essentiality of portal vein receptors in hypoglycemic counterregulation: direct proof via denervation in male canines.