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Insulin Protects against Hepatic Bioenergetic Deterioration Induced by Cancer Cachexia: An in Vivo ³¹P Magnetic Resonance Spectroscopy Study

Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1 [M. B.], and Department of Surgery and Nuclear Medicine, Victoria Hospital [R. I. I., G. B., A. A. D.], and Department of Nuclear Medicine and Magnetic Resonance, Lawson Research Institute, St. Joseph's Health Care Centre, The University of Western Ontario [G. D. M., R. T. T.], London, Ontario, Canada N6G 3V4

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo ³¹P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and ³¹P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of P₁ to ATP obtained from the hepatic ³¹P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a P_i/ATP ratio of 1.41 ± 0.35 (SE), significantly higher (P < 0.05) than the P_i/ATP ratio for short-term or chronic insulin treatment groups (P_i/ATP 0.92 ± 0.22 and 0.84 ± 0.22, respectively) or rats before tumor implantation (P_i/ATP 0.76 ± 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.

¹ To whom requests for reprints should be addressed, at Department of Surgery, Victoria Hospital, 375 South Street, London, Ontario, Canada N6G 3V4.

Received 6/ 2/94. Accepted 10/12/94.

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