Divergent effects of insulin on insulin-like growth factor-II gene expression in the rat hypothalamus.
The effect of peripheral insulin treatment on brain content and synthesis of insulin-like growth factor-II (IGF-II) was studied in acute and chronic conditions. After a 3-h hyperinsulinemic/euglycemic clamp, rats were killed, and brains were removed for IGF-II analysis. Insulin infusion elevated IGF-II concentrations in the dorsomedial hypothalamus (DMH) and suprachiasmatic nucleus, but decreased IGF-II in the paraventricular nucleus, lateral hypothalamus (LtH), and supraoptic nucleus compared to values in control animals. In separate parallel studies, the effects of 4 days of insulin injection (1 U insulin/rat, sc, twice daily) on brain IGF-II mRNA and peptide were determined. For RNA analysis the hypothalamus was divided into three regions (lateral, ventral, and dorsal). IGF-II mRNA content was shown to vary by an order of magnitude within the adult rat hypothalamus under control conditions, and there appeared to be a differential region-dependent response to insulin treatment. Relative abundance of IGF-II mRNA in control hypothalami was VH much greater than cortex greater than or equal to LtH greater than DMH. IGF-II mRNA content declined after insulin treatment in the VH, but rose in all other regions. Insulin increased IGF-II peptide content in the paraventricular nucleus, LtH, and VMH but decreased IGF-II in the DMH and suprachiasmatic nucleus. These results indicate that peripheral insulin status may be an important factor in the synthesis and secretion of IGF-II in the brain.
Department of Internal Medicine, Virginia Medical School, Norfolk 23501.
T J
TJ
Lauterio
P F
PF
Aravich
P
P
Rotwein
D000818:Animals; D001345:Autoradiography; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000502:physiology*; D007120:Immunochemistry; D007328:Insulin / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution
D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II