Deficits in reproductive behavior in diabetic female rats are due to hypoinsulinemia rather than hyperglycemia.
These studies determined whether deficits in reproductive behavior observed in streptozotocin (STZ)-induced diabetic female rats are caused by hyperglycemia or loss of insulin. Female Sprague-Dawley rats were ovariectomized and made diabetic by a single ip injection of STZ (75 mg/kg). Reproductive behavior was measured 12 days after the onset of hyperglycemia following the injection of estrogen and progesterone in doses known to restore reproductive behavior in nondiabetic rats. Rats in which STZ produced diabetes showed significantly reduced receptive and proceptive sexual behaviors. Normalization of blood glucose levels either by restricting diet or by phlorizin treatment failed to restore reproductive behavior in diabetic animals. However, even doses of insulin which were not fully effective in correcting peripheral hyperglycemia were able to prevent the STZ-induced behavioral deficit. No changes in general activity were observed in any experimental group as assessed by open field activity. The density of the norepinephrine transporter, as measured by [3H]nisoxetine binding, was reduced in the cortex but not in the brain stem, hypothalamus, or hippocampus of diabetic animals. Insulin treatment prevented the loss of cortical [3H]nisoxetine binding, and even partial normalization of blood glucose restored cortical [3H]nisoxetine binding to control levels. These findings suggest that diabetes-induced reproductive deficits are due to hypoinsulinemia and cannot be corrected simply by the normalization of blood glucose, whereas reductions in the density of cortical norepinephrine transporter result from hyperglycemia.
Karkanias
G B
GB
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Morales
J C
JC
Li
C S
CS
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D002352:Carrier Proteins / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D007328:Insulin / Q000097:blood*; D007989:Libido / Q000502:physiology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000502:physiology*; D027981:Symporters
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D027981:Symporters