PMID- 10078560
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 3
DP  - 1999 Mar
TI  - Chronic hypoglycemia and diabetes impair counterregulation induced by localized 
      2-deoxy-glucose perfusion of the ventromedial hypothalamus in rats.
PG  - 584-7
AB  - Previous studies have demonstrated that the ventromedial hypothalamus (VMH) plays 
      a critical role in sensing and responding to systemic hypoglycemia. To evaluate 
      the mechanisms of defective counterregulation caused by iatrogenic hypoglycemia 
      and diabetes per se, we delivered 2-deoxy-glucose (2-DG) via microdialysis into 
      the VMH to produce localized cellular glucopenia in the absence of systemic 
      hypoglycemia. Three groups of awake chronically catheterized rats were studied: 
      1) nondiabetic (with a mean daily glucose [MDG] of 6.9 mmol/l) BB control rats (n 
      = 5); 2) chronically hypoglycemic nondiabetic (3-4 weeks, with an MDG of 2.7 
      mmol/l) BB rats (n = 5); and 3) moderately hyperglycemic insulin-treated diabetic 
      (with an MDG of 12.4 mmol/l) BB rats (n = 8). In hypoglycemic rats, both glucagon 
      and catecholamine responses to VMH glucopenia were markedly (77-93%) suppressed. 
      In diabetic rats, VMH 2-DG perfusion was totally ineffective in stimulating 
      glucagon release. The epinephrine response, but not the norepinephrine response, 
      was also diminished by 38% in the diabetic group. We conclude that impaired 
      counterregulation after chronic hypoglycemia may result from alterations of the 
      VMH or its efferent pathways. In diabetes, the capacity of VMH glucopenia to 
      activate the sympathoadrenal system is only modestly diminished; however, the 
      communication between the VMH and the alpha-cell is totally interrupted.
FAU - Borg, M A
AU  - Borg MA
AD  - Department of Internal Medicine, Howard Hughes Medical Institute, Yale University 
      School of Medicine, New Haven, Connecticut 06520-8020, USA.
FAU - Borg, W P
AU  - Borg WP
FAU - Tamborlane, W V
AU  - Tamborlane WV
FAU - Brines, M L
AU  - Brines ML
FAU - Shulman, G I
AU  - Shulman GI
FAU - Sherwin, R S
AU  - Sherwin RS
LA  - eng
GR  - R01 DK040936/DK/NIDDK NIH HHS/United States
GR  - P30-DK-45735/DK/NIDDK NIH HHS/United States
GR  - R01-DK-20495/DK/NIDDK NIH HHS/United States
GR  - R01-DK-40936/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 9007-92-5 (Glucagon)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Deoxyglucose/administration & dosage/*pharmacology
MH  - Diabetes Mellitus, Type 1/blood/*physiopathology
MH  - Epinephrine/blood
MH  - Glucagon/blood
MH  - Homeostasis
MH  - Hypoglycemia/*physiopathology
MH  - Male
MH  - Microdialysis
MH  - Norepinephrine/blood
MH  - Perfusion
MH  - Rats
MH  - Rats, Inbred BB
MH  - Ventromedial Hypothalamic Nucleus/drug effects/physiology/*physiopathology
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - 10.2337/diabetes.48.3.584 [doi]
PST - ppublish
SO  - Diabetes. 1999 Mar;48(3):584-7. doi: 10.2337/diabetes.48.3.584.