The Medial Amygdalar Nucleus

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

Ligang Zhou, Nina Podolsky, Zhen Sang, Yuyan Ding, Xiaoning Fan, Qingchun Tong, Barry E. Levin, Rory J. McCrimmon (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    36 Citations (Scopus)

    Abstract

    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.

    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).

    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.

    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

    Original languageEnglish
    Pages (from-to)2646-2652
    Number of pages7
    JournalDiabetes
    Volume59
    Issue number10
    DOIs
    Publication statusPublished - Oct 2010

    Keywords

    • INDUCED HORMONAL COUNTERREGULATION
    • VENTROMEDIAL HYPOTHALAMUS
    • BLOOD-GLUCOSE
    • PROJECTION NEURONS
    • ACCUMBENS NUCLEUS
    • FACTOR RECEPTORS
    • RAT-BRAIN
    • GLUCOKINASE
    • EXPRESSION
    • LOCALIZATION

    Cite this

    Zhou, Ligang ; Podolsky, Nina ; Sang, Zhen ; Ding, Yuyan ; Fan, Xiaoning ; Tong, Qingchun ; Levin, Barry E. ; McCrimmon, Rory J. / The Medial Amygdalar Nucleus : A Novel Glucose-Sensing Region That Modulates the Counterregulatory Response to Hypoglycemia. In: Diabetes. 2010 ; Vol. 59, No. 10. pp. 2646-2652.
    @article{6e481b95f5cc49bfb22a57f74adb569d,
    title = "The Medial Amygdalar Nucleus: A Novel Glucose-Sensing Region That Modulates the Counterregulatory Response to Hypoglycemia",
    abstract = "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.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).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.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",
    keywords = "INDUCED HORMONAL COUNTERREGULATION, VENTROMEDIAL HYPOTHALAMUS, BLOOD-GLUCOSE, PROJECTION NEURONS, ACCUMBENS NUCLEUS, FACTOR RECEPTORS, RAT-BRAIN, GLUCOKINASE, EXPRESSION, LOCALIZATION",
    author = "Ligang Zhou and Nina Podolsky and Zhen Sang and Yuyan Ding and Xiaoning Fan and Qingchun Tong and Levin, {Barry E.} and McCrimmon, {Rory J.}",
    year = "2010",
    month = "10",
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    The Medial Amygdalar Nucleus : A Novel Glucose-Sensing Region That Modulates the Counterregulatory Response to Hypoglycemia. / Zhou, Ligang; Podolsky, Nina; Sang, Zhen; Ding, Yuyan; Fan, Xiaoning; Tong, Qingchun; Levin, Barry E.; McCrimmon, Rory J. (Lead / Corresponding author).

    In: Diabetes, Vol. 59, No. 10, 10.2010, p. 2646-2652.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The Medial Amygdalar Nucleus

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

    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 - 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.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).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.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

    AB - 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.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).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.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

    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

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    U2 - 10.2337/db09-0995

    DO - 10.2337/db09-0995

    M3 - Article

    VL - 59

    SP - 2646

    EP - 2652

    JO - Diabetes

    JF - Diabetes

    SN - 0012-1797

    IS - 10

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