The Medial Amygdalar Nucleus

TY - JOUR

T1 - The Medial Amygdalar Nucleus

T2 - A Novel Glucose-Sensing Region That Modulates the Counterregulatory Response to Hypoglycemia

A1 - Zhou,Ligang

A1 - Podolsky,Nina

A1 - Sang,Zhen

A1 - Ding,Yuyan

A1 - Fan,Xiaoning

A1 - Tong,Qingchun

A1 - Levin,Barry E.

A1 - McCrimmon,Rory J.

AU - Zhou,Ligang

AU - Podolsky,Nina

AU - Sang,Zhen

AU - Ding,Yuyan

AU - Fan,Xiaoning

AU - Tong,Qingchun

AU - Levin,Barry E.

AU - McCrimmon,Rory J.

PY - 2010/10

Y1 - 2010/10

N2 - <p>OBJECTIVE-To determine whether the medial amygdalar nucleus (MAN) represents a novel brain glucose-sensing region involved in the detection of hypoglycemia and generation of a counterregulatory hormone response.</p><p>RESEARCH DESIGN AND METHODS-Fura-2 calcium imaging was used to assess glucose responsivity in neurons isolated from the MAN and single-cell real-time reverse transcription PCR used to examine gene expression within glucose-responsive neurons. In vivo studies with local MAN perfusion of the glucoprivic agent, 2-deoxyglucose (2-DG), under normal and hypoglycemic conditions and also after MAN lesioning with ibotenic acid, were used to examine the functional role of MAN glucose sensors. In addition, retrograde neuronal tracer studies were used to examine reciprocal pathways between the MAN and the ventromedial hypothalamus (VMH).</p><p>RESULTS-The MAN contains a population of glucose-sensing neurons (13.5%), which express glucokinase, and the selective urocortin 3 (UCN3) receptor CRH-R2, but not UCN3 itself. Lesioning the MAN suppressed, whereas 2-DG infusion amplified, the counterregulatory response to hyperinsulinemic hypoglycemia in vivo. However, 2-DG infusion to the MAN or VMH under normoglycemic conditions had no systemic effect. The VMH is innervated by UCN3 neurons that arise mainly from the MAN, and similar to 1/3 of MAN UCN3 neurons are active during mild hypoglycemia.</p><p>CONCLUSIONS-The MAN represents a novel limbic glucose-sensing region that contains characteristic glucokinase-expressing glucose-sensing neurons that respond directly to manipulations of glucose availability both in vitro and in vivo. Moreover, UCN3 neurons may provide feedback inhibitory regulation of the counterregulatory response through actions within the VMH and the MAN. Diabetes 59:2646-2652, 2010</p>

AB - <p>OBJECTIVE-To determine whether the medial amygdalar nucleus (MAN) represents a novel brain glucose-sensing region involved in the detection of hypoglycemia and generation of a counterregulatory hormone response.</p><p>RESEARCH DESIGN AND METHODS-Fura-2 calcium imaging was used to assess glucose responsivity in neurons isolated from the MAN and single-cell real-time reverse transcription PCR used to examine gene expression within glucose-responsive neurons. In vivo studies with local MAN perfusion of the glucoprivic agent, 2-deoxyglucose (2-DG), under normal and hypoglycemic conditions and also after MAN lesioning with ibotenic acid, were used to examine the functional role of MAN glucose sensors. In addition, retrograde neuronal tracer studies were used to examine reciprocal pathways between the MAN and the ventromedial hypothalamus (VMH).</p><p>RESULTS-The MAN contains a population of glucose-sensing neurons (13.5%), which express glucokinase, and the selective urocortin 3 (UCN3) receptor CRH-R2, but not UCN3 itself. Lesioning the MAN suppressed, whereas 2-DG infusion amplified, the counterregulatory response to hyperinsulinemic hypoglycemia in vivo. However, 2-DG infusion to the MAN or VMH under normoglycemic conditions had no systemic effect. The VMH is innervated by UCN3 neurons that arise mainly from the MAN, and similar to 1/3 of MAN UCN3 neurons are active during mild hypoglycemia.</p><p>CONCLUSIONS-The MAN represents a novel limbic glucose-sensing region that contains characteristic glucokinase-expressing glucose-sensing neurons that respond directly to manipulations of glucose availability both in vitro and in vivo. Moreover, UCN3 neurons may provide feedback inhibitory regulation of the counterregulatory response through actions within the VMH and the MAN. Diabetes 59:2646-2652, 2010</p>

KW - INDUCED HORMONAL COUNTERREGULATION

KW - VENTROMEDIAL HYPOTHALAMUS

KW - BLOOD-GLUCOSE

KW - PROJECTION NEURONS

KW - ACCUMBENS NUCLEUS

KW - FACTOR RECEPTORS

KW - RAT-BRAIN

KW - GLUCOKINASE

KW - EXPRESSION

KW - LOCALIZATION

U2 - 10.2337/db09-0995

DO - 10.2337/db09-0995

M1 - Article

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

VL - 59

SP - 2646

EP - 2652

ER -