Portal vein hypoglycemia is essential for full induction of hypoglycemia-associated autonomic failure with slow-onset hypoglycemia

Aleksey V Matveyenko, MaryAnn Bohland, Maziyar Saberi, Casey M. Donovan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Antecedent hypoglycemia leads to impaired counterregulation and hypoglycemic un-awareness. To ascertain whether antecedent portal vein hypoglycemia impairs portal vein glucose sensing, thereby inducing counterregulatory failure, we compared the effects of antecedent hypoglycemia, with and without normalization of portal vein glycemia, upon the counterregulatory response to subsequent hypoglycemia. Male Wistar rats were chronically cannulated in the carotid artery (sampling), jugular vein (glucose and insulin infusion), and mesenteric vein (glucose infusion). On day 1, the following three distinct antecedent protocols were employed: 1) HYPO-HYPO: systemic hypoglycemia (2.52 ± 0.11 mM); 2) HYPO-EUG: systemic hypoglycemia (2.70 ± 0.03 mM) with normalization of portal vein glycemia (portal vein glucose = 5.86 ± 0.10 mM); and 3) EUG-EUG: systemic euglycemia (6.33 ± 0.31 mM). On day 2, all groups underwent a hyperinsulinemic-hypoglycemic clamp in which the fall in glycemia was controlled so as to reach the nadir (2.34 ± 0.04 mM) by minute 75. Counterregulatory hormone responses were measured at basal (-30 and 0) and during hypoglycemia (60-105 min). Compared with EUG-EUG, antecedent hypoglycemia (HYPO-HYPO) significantly blunted the peak epinephrine (10.44 ± 1.35 vs. 15.75 ± 1.33 nM: P = 0.01) and glucagon (341 ± 16 vs. 597 ± 82 pg/ml: P = 0.03) responses to next-day hypoglycemia. Normalization of portal glycemia during systemic hypoglycemia on day 1 (HYPO-EUG) prevented blunting of the peak epinephrine (15.59 ± 1.43 vs. 15.75 ± 1.33 nM: P = 0.94) and glucagon (523 ± 169 vs. 597 ± 82 pg/ml: P = 0.66) responses to day 2 hypoglycemia. Consistent with hormonal responses, the glucose infusion rate during day 2 hypoglycemia was substantially elevated in HYPO-HYPO (74 ± 12 vs. 49 ± 4 μmol·kg -1·min-1; P = 0.03) but not HYPO-EUG (39 ± 7 vs. 49 ± 4 μmol·kg-1·min-1: P = 0.36). Antecedent hypoglycemia local to the portal vein is required for the full induction of hypoglycemia-associated counterregulatory failure with slow-onset hypoglycemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume293
Issue number3
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

Portal Vein
Hypoglycemia
Glucose
Glucagon
Hypoglycemic Agents
Epinephrine
Clamping devices
Rats
Hormones
Insulin
Sampling
Mesenteric Veins
Jugular Veins
Carotid Arteries
Wistar Rats

Keywords

  • Counterregulation
  • Glucose sensor
  • Sympathoadrenal

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

@article{73bc4764be31431a90f99f5fbe99500c,
title = "Portal vein hypoglycemia is essential for full induction of hypoglycemia-associated autonomic failure with slow-onset hypoglycemia",
abstract = "Antecedent hypoglycemia leads to impaired counterregulation and hypoglycemic un-awareness. To ascertain whether antecedent portal vein hypoglycemia impairs portal vein glucose sensing, thereby inducing counterregulatory failure, we compared the effects of antecedent hypoglycemia, with and without normalization of portal vein glycemia, upon the counterregulatory response to subsequent hypoglycemia. Male Wistar rats were chronically cannulated in the carotid artery (sampling), jugular vein (glucose and insulin infusion), and mesenteric vein (glucose infusion). On day 1, the following three distinct antecedent protocols were employed: 1) HYPO-HYPO: systemic hypoglycemia (2.52 ± 0.11 mM); 2) HYPO-EUG: systemic hypoglycemia (2.70 ± 0.03 mM) with normalization of portal vein glycemia (portal vein glucose = 5.86 ± 0.10 mM); and 3) EUG-EUG: systemic euglycemia (6.33 ± 0.31 mM). On day 2, all groups underwent a hyperinsulinemic-hypoglycemic clamp in which the fall in glycemia was controlled so as to reach the nadir (2.34 ± 0.04 mM) by minute 75. Counterregulatory hormone responses were measured at basal (-30 and 0) and during hypoglycemia (60-105 min). Compared with EUG-EUG, antecedent hypoglycemia (HYPO-HYPO) significantly blunted the peak epinephrine (10.44 ± 1.35 vs. 15.75 ± 1.33 nM: P = 0.01) and glucagon (341 ± 16 vs. 597 ± 82 pg/ml: P = 0.03) responses to next-day hypoglycemia. Normalization of portal glycemia during systemic hypoglycemia on day 1 (HYPO-EUG) prevented blunting of the peak epinephrine (15.59 ± 1.43 vs. 15.75 ± 1.33 nM: P = 0.94) and glucagon (523 ± 169 vs. 597 ± 82 pg/ml: P = 0.66) responses to day 2 hypoglycemia. Consistent with hormonal responses, the glucose infusion rate during day 2 hypoglycemia was substantially elevated in HYPO-HYPO (74 ± 12 vs. 49 ± 4 μmol·kg -1·min-1; P = 0.03) but not HYPO-EUG (39 ± 7 vs. 49 ± 4 μmol·kg-1·min-1: P = 0.36). Antecedent hypoglycemia local to the portal vein is required for the full induction of hypoglycemia-associated counterregulatory failure with slow-onset hypoglycemia.",
keywords = "Counterregulation, Glucose sensor, Sympathoadrenal",
author = "Matveyenko, {Aleksey V} and MaryAnn Bohland and Maziyar Saberi and Donovan, {Casey M.}",
year = "2007",
month = "9",
doi = "10.1152/ajpendo.00283.2007",
language = "English (US)",
volume = "293",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Portal vein hypoglycemia is essential for full induction of hypoglycemia-associated autonomic failure with slow-onset hypoglycemia

AU - Matveyenko, Aleksey V

AU - Bohland, MaryAnn

AU - Saberi, Maziyar

AU - Donovan, Casey M.

PY - 2007/9

Y1 - 2007/9

N2 - Antecedent hypoglycemia leads to impaired counterregulation and hypoglycemic un-awareness. To ascertain whether antecedent portal vein hypoglycemia impairs portal vein glucose sensing, thereby inducing counterregulatory failure, we compared the effects of antecedent hypoglycemia, with and without normalization of portal vein glycemia, upon the counterregulatory response to subsequent hypoglycemia. Male Wistar rats were chronically cannulated in the carotid artery (sampling), jugular vein (glucose and insulin infusion), and mesenteric vein (glucose infusion). On day 1, the following three distinct antecedent protocols were employed: 1) HYPO-HYPO: systemic hypoglycemia (2.52 ± 0.11 mM); 2) HYPO-EUG: systemic hypoglycemia (2.70 ± 0.03 mM) with normalization of portal vein glycemia (portal vein glucose = 5.86 ± 0.10 mM); and 3) EUG-EUG: systemic euglycemia (6.33 ± 0.31 mM). On day 2, all groups underwent a hyperinsulinemic-hypoglycemic clamp in which the fall in glycemia was controlled so as to reach the nadir (2.34 ± 0.04 mM) by minute 75. Counterregulatory hormone responses were measured at basal (-30 and 0) and during hypoglycemia (60-105 min). Compared with EUG-EUG, antecedent hypoglycemia (HYPO-HYPO) significantly blunted the peak epinephrine (10.44 ± 1.35 vs. 15.75 ± 1.33 nM: P = 0.01) and glucagon (341 ± 16 vs. 597 ± 82 pg/ml: P = 0.03) responses to next-day hypoglycemia. Normalization of portal glycemia during systemic hypoglycemia on day 1 (HYPO-EUG) prevented blunting of the peak epinephrine (15.59 ± 1.43 vs. 15.75 ± 1.33 nM: P = 0.94) and glucagon (523 ± 169 vs. 597 ± 82 pg/ml: P = 0.66) responses to day 2 hypoglycemia. Consistent with hormonal responses, the glucose infusion rate during day 2 hypoglycemia was substantially elevated in HYPO-HYPO (74 ± 12 vs. 49 ± 4 μmol·kg -1·min-1; P = 0.03) but not HYPO-EUG (39 ± 7 vs. 49 ± 4 μmol·kg-1·min-1: P = 0.36). Antecedent hypoglycemia local to the portal vein is required for the full induction of hypoglycemia-associated counterregulatory failure with slow-onset hypoglycemia.

AB - Antecedent hypoglycemia leads to impaired counterregulation and hypoglycemic un-awareness. To ascertain whether antecedent portal vein hypoglycemia impairs portal vein glucose sensing, thereby inducing counterregulatory failure, we compared the effects of antecedent hypoglycemia, with and without normalization of portal vein glycemia, upon the counterregulatory response to subsequent hypoglycemia. Male Wistar rats were chronically cannulated in the carotid artery (sampling), jugular vein (glucose and insulin infusion), and mesenteric vein (glucose infusion). On day 1, the following three distinct antecedent protocols were employed: 1) HYPO-HYPO: systemic hypoglycemia (2.52 ± 0.11 mM); 2) HYPO-EUG: systemic hypoglycemia (2.70 ± 0.03 mM) with normalization of portal vein glycemia (portal vein glucose = 5.86 ± 0.10 mM); and 3) EUG-EUG: systemic euglycemia (6.33 ± 0.31 mM). On day 2, all groups underwent a hyperinsulinemic-hypoglycemic clamp in which the fall in glycemia was controlled so as to reach the nadir (2.34 ± 0.04 mM) by minute 75. Counterregulatory hormone responses were measured at basal (-30 and 0) and during hypoglycemia (60-105 min). Compared with EUG-EUG, antecedent hypoglycemia (HYPO-HYPO) significantly blunted the peak epinephrine (10.44 ± 1.35 vs. 15.75 ± 1.33 nM: P = 0.01) and glucagon (341 ± 16 vs. 597 ± 82 pg/ml: P = 0.03) responses to next-day hypoglycemia. Normalization of portal glycemia during systemic hypoglycemia on day 1 (HYPO-EUG) prevented blunting of the peak epinephrine (15.59 ± 1.43 vs. 15.75 ± 1.33 nM: P = 0.94) and glucagon (523 ± 169 vs. 597 ± 82 pg/ml: P = 0.66) responses to day 2 hypoglycemia. Consistent with hormonal responses, the glucose infusion rate during day 2 hypoglycemia was substantially elevated in HYPO-HYPO (74 ± 12 vs. 49 ± 4 μmol·kg -1·min-1; P = 0.03) but not HYPO-EUG (39 ± 7 vs. 49 ± 4 μmol·kg-1·min-1: P = 0.36). Antecedent hypoglycemia local to the portal vein is required for the full induction of hypoglycemia-associated counterregulatory failure with slow-onset hypoglycemia.

KW - Counterregulation

KW - Glucose sensor

KW - Sympathoadrenal

UR - http://www.scopus.com/inward/record.url?scp=34548420968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548420968&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00283.2007

DO - 10.1152/ajpendo.00283.2007

M3 - Article

C2 - 17638706

AN - SCOPUS:34548420968

VL - 293

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3

ER -