Hypothalamic Axis Ups Glucose Tolerance Via Glycosuria
Hypothalamic-sympathetic nervous system-renal axis ID'd that regulates tubular glucose reabsorption
TUESDAY, Oct. 20, 2015 (HealthDay News) -- A previously unrecognized hypothalamic-sympathetic nervous system (SNS)-renal axis has been identified that may impact glucose homeostasis, according to an experimental study published online Oct. 14 in Diabetes.
Kavaljit H. Chhabra, M.Pharm., Ph.D., from the University of Michigan Medical School in Ann Arbor, and colleagues examined the role of hypothalamic proopiomelanocortin (POMC)-deficiency in glucose homeostasis.
Although hypothalamic arcuate nucleus (Arc) POMC-deficient mice develop severe obesity and insulin resistance, the researchers found that these mice unexpectedly exhibited improved glucose tolerance and remained protected from hyperglycemia. An insulin-independent pathway was suggested as responsible for the enhanced glucose tolerance. Compared with wildtype controls, mutant mice demonstrated elevated glucose effectiveness and exaggerated glycosuria at comparable blood glucose concentrations. In mutant mice, central administration of the melanocortin receptor agonist melanotan II reversed their alterations in glucose tolerance and glycosuria; conversely, administration of the antagonist Agrp enhanced glucose tolerance in wildtype mice. ArcPOMC-deficient mice had glycosuria that was due to decreased levels of renal glucose transporter 2 (rGLUT2), but not sodium/glucose cotransporter 2, and correlated with decreased renal catecholamine content. The genotype-differences in glucose tolerance and rGLUT2 levels were abolished by epinephrine treatment, indicating that the underlying mechanism was reduced renal SNS activity.
"The ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes," the authors write.