Counterregulation during hypoglycemia is directed by widespread brain regions.
Previous studies have demonstrated the importance of the brain in directing counterregulation during insulin-induced hypoglycemia in dogs. The capability of selective carotid or vertebrobasilar hypoglycemia in triggering counterregulation was assessed in this study using overnight-fasted dogs. Insulin (21 pM.kg-1.min-1) was infused for 3 h to create peripheral hypoglycemia in the presence of 1) selective carotid hypoglycemia (vertebral glucose infusion, n = 5), 2) selective vertebrobasilar hypoglycemia (carotid glucose infusion, n = 5), 3) the absence of brain hypoglycemia (carotid and vertebral glucose infusion, n = 4), or 4) total brain hypoglycemia (no head glucose infusion, n = 5). Glucose was infused via a leg vein as needed in each group to minimize the differences in peripheral glucose levels (2.6 +/- 0.1, 3.0 +/- 0.2, 2.7 +/- 0.1, and 2.5 +/- 0.1 mM, respectively). The humoral responses (cortisol, glucagon, catecholamines, and pancreatic polypeptide) to hypoglycemia were minimally attenuated (< 40%) by selective carotid or vertebrobasilar euglycemia. In addition, the increase in hepatic glucose production, as assessed using [3-3H]glucose, was attenuated by only 41 and 34%, respectively, during selective carotid or vertebrobasilar hypoglycemia. These observations offer support for the hypothesis that more than one center is important in hypoglycemic counterregulation in the dog and that they are located in brain regions supplied by the carotid and vertebrobasilar arteries, because significant counterregulation occurred when hypoglycemia developed in either of these circulations. Counterregulation during hypoglycemia, therefore, is probably directed by widespread brain regions that contain glucose-sensitive neurons such that the sensing sites are redundant.
Frizzell
R T
RT
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615.
Jones
E M
EM
Davis
S N
SN
Biggers
D W
DW
Myers
S R
SR
Connolly
C C
CC
Neal
D W
DW
Jaspan
J B
JB
Cherrington
A D
AD
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D002339:Carotid Arteries / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood; D014711:Vertebral Artery / Q000503:physiopathology
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D006854:Hydrocortisone