Insulin and Steatonecrosis: Are They Related?

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Abstract
Hepatic steatosis and steatonecrosis occur in non–alcoholic individuals, usually in a setting of obesity, type II diabetes mellitus, and after jejunoileal bypass. We propose an hypothesis for the pathogenesis of these hepaic lesions based on an observation in peritoneal dialysis patients. Hepatic histology was examined at autopsy in eleven patients with type I diabetes mellitus and renal failure who had received intraperitoneal insulin in conjunction with continuous ambulatory perritoneal dialysis (CAPD). Steatosis in a unique subcapsular distribution occurred in 10 of 11 patients treated with intraperitoneal insulin and in none of 9 controls receiving CAPD without insulin. Three of the 11 had steatonecrosis, 2 of whom had Mallory bodies. We suggest that isulin has an important role in the pathogenesis of steatosis and steatoncrosis. In CAPD patients the lesions occurred only under the capsule where concentrations of insulin are high secondary to its intraperitoneal administration. In obese patients the lesions occur throughhout the liver where insulin concentrations are high because of elevated levels in the portal vein. Free fatty acids (FFA) are oxidized in the liver by a pathway that is blocked by insulin. In the presence of insulin, FFA are preferentially esterified into triglycerides which accumulate in large quantities leading to steatosis; small amounts of FFA escaping local control may lead to membrane injury and steatonecrosis. Steatosis and/or steatonecrosis will occur when there is insulin secretion sufficient to block FFA oxidation but not sufficient to block FFA mobilization from adipose tissue. This situation occurs in obesity associated with type II diabetes where adipose tissues are resistant to insulin, and in obesity after jejunoileal–bypass where continued eating and insulin secretion occurs in the face of marked weight loss.