Insulin is ubiquitous in extrapancreatic tissues of rats and humans.

Abstract

Insulin has been detected, at levels higher than those in plasma, in a broad range of extrapancreatic tissues in both rats and humans. Rat liver insulin was shown to be indistinguishable from genuine insulin by radioimmunoassay, Sephadex chromatography, bioassay, and antibody neutralization. Liver insulin (like brain insulin) was unchanged in ob/ob mice, in rats treated with streptozotocin, or in fasted rats, despite marked alterations in pancreatic secretion of insulin and in liver content of insulin receptors. Insulin was found in cultured human IM-9 lymphocytes and cultured fibroblasts at concentrations greater than 100 times the levels in the media. IM-9 lymphocyte insulin also was shown to be indistinguishable from genuine insulin, by the same criteria used for liver insulin. The insulin concentration in cultured human cells was unaffected by depletion of insulin from the culture medium or by addition of beef insulin to the medium. The data suggest that a part, if not all, of the extrapancreatic tissue insulin is independent of plasma insulin and may be synthesized by the tissues themselves.Recently, we demonstrated the presence of insulint in the brain in concentrations higher than in plasma (1). This brain insulin was indistinguishable from genuine insulin by multiple criteria, and its tissue concentration did not vary at all with extreme changes in plasma insulin (2). In the present study we show that insulin immunoreactivity is present in essentially all tissues of humans and rats as well as in cultured lymphocytes and fibroblasts at concentrations that are 2-100 times those present in the plasma or culture medium. The material is similar to (or identical with) genuine insulin by radioimmunoassay, gel filtration, bioassay, and antibody neutralization. The concentration of cellular insulin in vio changes little or not at all in response to extremes of hyperinsulinemia and hypoinsulinemia. MATERIALS AND METHODSTissue Preparations. Male Sprague-Dawley rats (250-300 g) fed ad lib were decapitated between 1400 and 1600 hr; "fasted rats" had been denied food for 50-72 hr before they were killed. Rats injected with streptozotocin (65 mg/kg intravenously) and control rats (injected with isotonic saline) were sacrificed 1 month after treatment. Obese (ob/ob) mice and their thin littermates (mixtures of ob/+ and +/+) of the C57BL65 strain were killed at 8-10 weeks of age. Organs and plasma were collected and stored as reported (1, 2).Human tissue samples, obtained either during operations or at autopsy within 3 hr after death, were frozen on dry ice prior to extraction. Whole blood (500 ml) from a fasting (overnight) normal human volunteer was separated into mononuclear and granulocytic fractions by a modification (3) of the method of The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 572Boyum (4). The cells were washed in phosphate-buffered salin...

Evaluation of rat insulin messenger RNA in pancreatic and extrapancreatic tissues

“…This compared to 1500 pg of insulin mRNA per l-tg of pancreatic mRNA. Havrankova et al [41 and Rozensweig et al [21] have presented data to show that levels of insulin in brain are about 20 ng/gm of tissue, as compared to 40 p,g/gm of pancreas. Because the level of mRNA coding for a protein is roughly proportional to the amount of protein synthesized [29,30,32] one would estimate insulin mRNA in brain to be 2000-fold less abundant than in pancreas.…”

“…R N A was isolated from several organs of rats which had been reported to contain levels of insulin greater than plasma including liver, spleen, kidney, testes, and brain [21]. To look for proinsulin m R N A in extrapancreatic tissues, polyadenylated m R N A was enriched approximately 50-fold by oligo dT-cellulose chromatography.…”

Comparative Analysis of Insulin Gene Promoters

“…Low levels of extrapancreatic insulin have been detected in a number of other tissues (17,18) including brain (19), thymus (20 -22), lachrymal glands (23), and salivary glands (24). The role of insulin expression in non-␤-cells is unclear.…”

Insulin and insulin receptors in rodent brain

“…They all originate from the same zygote, have the same genetic complement and a ]potential capability to synthesize all proteins of that species. Recently, we found insulin in significant concentrations in essentially all mammalian tissues [24]. Why is insulin so widely distributed in the organis, m?…”