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Changes in Insulin, Somatostatin, and Glucagon Secretion during the Development of Obesity in Ventromedial Hypothalamic-Lesioned Rats^*

Second Division, Department of Medicine, Kyoto University School of Medicine Kyoto, Japan
The Diabetes Center, Ikeda Clinic Amagasaki, Japan

Address requests for reprints to: Yutaka Seino, M.D., Second Division of Internal Medicine, Kyoto University Faculty of Medicine, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.

Abstract

Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in rats after ventromedial hypothalamic (VMH) lesions were evaluated by measuring fasting hormone levels and their secretion from the isolated perfused pancreas. Fasting peripheral insulin levels were not altered 1 week after the VMH lesions but became progressively elevated at 3–4, 8–9, and 11–12 weeks compared to the values in sham-operated and age-matched control rats. In the portal vein, insulin levels also progressively increased in VMHlesioned rats, but the portal-peripheral gradient of insulin in the later phase of VMH obesity was significantly lower than in the early phase after VMH lesions. On the contrary, the arginineinduced insulin release from the perfused pancreas was highest at 1 week and gradually decreased thereafter, although it continued to remain higher than that of controls. The perfusate somatostatin response to arginine also was exaggerated in the VMH-lesioned rats. However, both the peripheral glucagon level and the glucagon secretion from the perfused pancreas of the VMH-lesioned rats were not significantly different from the controls. These results show that VMH lesions result in an increased insulin and somatostatin secretion. Using the cyclically perfused liver in situ, we have found that the hepatic extraction rate of insulin is indeed reduced in rats 8–9 weeks after VMH lesioning, and so have at least partly accounted for the decreased portal-peripheral gradient of insulin in the later VMH postoperative phase. (Endocrinology 114: 457, 1984)

Footnotes

^* This study was supported in part by Research Grant 57570861 from the Ministry of Education, Science, and Culture of Japan.

Received January 6, 1983.

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