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1 Minnesota Obesity Center and Research Service, Veterans Affairs Medical Center, Minneapolis 55417; and 2 Department of Medicine and 3 Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota 55455
Effects of
streptozotocin (STZ)-induced diabetes and insulin on opioid peptide
gene expression were examined in rats. In experiment 1, three groups were administered STZ (75 mg/kg ip
single injection). Two groups were killed at either 2 or 4 wk. In the
third group, insulin treatment (7.0 IU/kg × 1 day for 3 wk) was
initiated 1 wk after STZ injection. STZ induced hyperphagia and reduced
weight gain. Insulin decreased food intake and increased body weight relative to diabetes. Proopiomelanocortin (POMC) mRNA in arcuate nucleus (Arc) and pituitary decreased in diabetes and normalized after
insulin treatment. Prodynorphin (proDyn) mRNA increased in diabetes and
normalized in the pituitary after insulin but not in the Arc. Diabetes
did not alter proenkephalin (proEnk) expression in the Arc or
pituitary, nor dynorphin
A1-17 or 
-endorphin in
paraventricular nucleus (PVN). 
-Melanocyte-stimulating hormone
(-MSH) peptide levels were decreased in the PVN and normalized following insulin treatment. Diabetes increased Arc neuropeptide Y
mRNA, and insulin suppressed this increase. In
experiment 2, insulin (2.5 IU/kg sc)
daily for 1 wk in normal rats increased Arc POMC mRNA, but not proDyn
and proEnk mRNA. These results suggest that Arc POMC expression and PVN
-MSH peptide levels decrease in diabetes. Also, insulin may
influence Arc and pituitary POMC activity in neurons that regulate
energy metabolism.
opioids; neuropeptide Y; -melanocyte-stimulating hormone; energy
balance; streptozotocin; proopiomelanocortin
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