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- Title
Intrahypothalamic Insulin Does Not Augment the Sympathoadrenal Response to Hypoglycemia.
- Authors
Ishihara, Kent K.; Haywood, Samuel; Puente, Erwin; Daphna-Iken, Dorit; Fisher, Simon J.
- Abstract
While it is well known that peripheral actions of insulin cause hypoglycemia, several studies suggest that insulin action in the brain may paradoxically protect against severe hypoglycemia by augmenting the sympathoadrenal (SA) response to hypoglycemia. Since the mediobasal hypothalamus has been identified as a key site for both glucose sensing and insulin action in the brain, we hypothesized that a direct infusion of insulin into this area would amplify the SA response to hypoglycemia. Nine week-old male Sprague-Dawley rats were implanted with bilateral intrahypothalamic (IH) cannulas and subsequent jugular vein and carotid artery catheters. After a one week recovery and an overnight fast, insulin (15 mU in 30 µd) or aCSF (control) was infused bilaterally into the mediobasal hypothalamus over 5 hours. During the final two hours of the IH infusion, we measured the SA response to either a hyperinsulinemic (5 mU/kg/min) hypoglycemic (∼50 mg/dl) clamp or to a single 600 mg/kg IV bolus of 2-deoxy-glucose (2-DG). The 2-DG experiments were designed to selectively increase IH insulin in the absence of marked peripheral hyperinsulinemia. Proper placement of the IH cannulas was confirmed by injection of Evan's Blue dye. In response to insulin-induced hypoglycemia, epinephrine (E) rose more than 60-fold in both the IH-control and the IH-insulin groups (3768±472 vs. 3224±313 pg/ml, P=NS), and norepinephrine (NE) increased more than 4-fold (850±97 vs. 653±79 pg/ml, P=NS). Similarly, in response to 2-DG-induced glucoprivation, E rose more than 60-fold in both the IH-control and IH-insulin groups (3920±580 vs. 3802±364 pg/ml, P=NS), and NE increased more than 4 fold (807±79 vs. 757±79 pg/ml, P=NS). In summary, we were surprised to find that IH insulin did not augment the SA response to insulin-induced hypoglycemia nor to 2-DG-induced glucoprivation in male Sprague-Dawley rats. We propose that the previously noted acute actions of insulin to augment the sympathoadrenal response to hypoglycemia are likely mediated via extrahypothalamic mechanisms.
- Subjects
INSULIN; HYPOGLYCEMIA; BRAIN; HYPOTHALAMUS; HYPOGLYCEMIC agents
- Publication
Diabetes, 2007, Vol 56, pA167
- ISSN
0012-1797
- Publication type
Article