Localization of glucokinase gene expression in the rat brain

Ron Lynch, Linda S. Tompkins, Heddwen L Brooks, Ambrose A. Dunn-Meynell, Barry E. Levin

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

The brain contains a subpopulation of glucosensing neurons that alter their firing rate in response to elevated glucose concentrations. In pancreatic β-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production. A similar role for GK is proposed to underlie neuronal glucosensing. Via in situ hybridization, GK mRNA was localized to hypothalamic areas that are thought to contain relatively large populations of glucosensing neurons (the arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the lateral area). GK also was found in brain areas without known glucosensing neurons (the lateral habenula, the bed nucleus stria terminalis, the inferior olive, the retrochiasmatic and medial preoptic areas, and the thalamic posterior paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei). Conversely, GK message was not found in the nucleus tractus solitarius, which contains glucosensing neurons, or in ependymal cells lining the third ventricle, where others have described its presence. In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK+ neurons also expressed KIR6.2 (the pore- forming subunit of the ATP-sensitive K+ channel). The anatomic distribution of GK mRNA was confirmed in micropunch samples of hypothalamus via reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequencing of the recovered PCR product indicated identity with nucleotides 1092-1411 (within exon 9 and 10) of hepatic and β-cell GK. The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK+ neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism.

Original languageEnglish (US)
Pages (from-to)693-700
Number of pages8
JournalDiabetes
Volume49
Issue number5
StatePublished - May 2000

Fingerprint

Glucokinase
Gene Expression
Brain
Neurons
Arcuate Nucleus of Hypothalamus
Messenger RNA
Nucleotides
Adenosine Triphosphate
Habenula
Mediodorsal Thalamic Nucleus
Glucose
Septal Nuclei
Polymerase Chain Reaction
Third Ventricle
Solitary Nucleus
Preoptic Area
Paraventricular Hypothalamic Nucleus
Neuropeptide Y
Glycolysis
Neuropeptides

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Lynch, R., Tompkins, L. S., Brooks, H. L., Dunn-Meynell, A. A., & Levin, B. E. (2000). Localization of glucokinase gene expression in the rat brain. Diabetes, 49(5), 693-700.

Localization of glucokinase gene expression in the rat brain. / Lynch, Ron; Tompkins, Linda S.; Brooks, Heddwen L; Dunn-Meynell, Ambrose A.; Levin, Barry E.

In: Diabetes, Vol. 49, No. 5, 05.2000, p. 693-700.

Research output: Contribution to journalArticle

Lynch, R, Tompkins, LS, Brooks, HL, Dunn-Meynell, AA & Levin, BE 2000, 'Localization of glucokinase gene expression in the rat brain', Diabetes, vol. 49, no. 5, pp. 693-700.
Lynch R, Tompkins LS, Brooks HL, Dunn-Meynell AA, Levin BE. Localization of glucokinase gene expression in the rat brain. Diabetes. 2000 May;49(5):693-700.
Lynch, Ron ; Tompkins, Linda S. ; Brooks, Heddwen L ; Dunn-Meynell, Ambrose A. ; Levin, Barry E. / Localization of glucokinase gene expression in the rat brain. In: Diabetes. 2000 ; Vol. 49, No. 5. pp. 693-700.
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