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Sex-Specific Control of Fat Mass and Counterregulation by Hypothalamic Glucokinase
- Source :
- Diabetes. 65(10)
- Publication Year :
- 2015
-
Abstract
- Glucokinase (Gck) is a critical regulator of glucose-induced insulin secretion by pancreatic β-cells. It has been suggested to also play an important role in glucose signaling in neurons of the ventromedial hypothalamic nucleus (VMN), a brain nucleus involved in the control of glucose homeostasis and feeding. To test the role of Gck in VMN glucose sensing and physiological regulation, we studied mice with genetic inactivation of the Gck gene in Sf1 neurons of the VMN (Sf1Gck−/− mice). Compared with control littermates, Sf1Gck−/− mice displayed increased white fat mass and adipocyte size, reduced lean mass, impaired hypoglycemia-induced glucagon secretion, and a lack of parasympathetic and sympathetic nerve activation by neuroglucopenia. However, these phenotypes were observed only in female mice. To determine whether Gck was required for glucose sensing by Sf1 neurons, we performed whole-cell patch clamp analysis of brain slices from control and Sf1Gck−/− mice. Absence of Gck expression did not prevent the glucose responsiveness of glucose-excited or glucose-inhibited Sf1 neurons in either sex. Thus Gck in the VMN plays a sex-specific role in the glucose-dependent control of autonomic nervous activity; this is, however, unrelated to the control of the firing activity of classical glucose-responsive neurons.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Patch-Clamp Techniques
Endocrinology, Diabetes and Metabolism
Hypothalamus
030209 endocrinology & metabolism
White adipose tissue
Biology
Glucagon
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Adipocyte
Internal medicine
Glucokinase
Internal Medicine
medicine
Adipocytes
Glucose homeostasis
Animals
Homeostasis
Neurons
Glucagon secretion
Mice, Mutant Strains
030104 developmental biology
Endocrinology
Glucose
chemistry
Ventromedial Hypothalamic Nucleus
Female
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 65
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....38dc38b6ae5b2f4bdf2bb62ea3b3ffd7