We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per c...

Insulin has been shown to inhibit rat growth hormone (GH) gene transcription. The effects of insulin were therefore tested on the expression of a transfected human GH gene. A 2.6-kilobase EcoRI fragment of the human GH gene was propagated in pUC18 and transfected by calcium-phosphate shock into HeLa and GC cells, respectively. Transfected cells grown in serum-free medium for 72 h expressed huma...

Using information gained from (i) the relative HPLC retention of an abnormal insulin present in the serum of a hyperinsulinemic diabetic patient and (ii) the loss of an Mbo II restriction site in one of the patient's insulin gene alleles, it was recently predicted that the mutant insulin contained a serine-for-phenylalanine substitution at position B24 or B25. We have now prepared human [SerB24...

In view of the lifelong exposure and large patient populations involved, insulin analogs with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogs may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogs are safe. In line with these findings, we observed th...

OBJECTIVE India's majority of patients-including those living with diabetes-seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. METHODS A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative inte...

Control of the expression of the human insulin-like growth factor II gene is known to be complex, displaying both tissue-specific and developmental regulation. Insulin-like growth factor II is expressed at high levels in most tissues in the human fetus and appears to be important in fetal growth. In adult life, high levels of expression are found chiefly in liver, kidney, skin, nerve, and muscl...

The aims of the study were to outline the sequence of events that gave rise to the vertebrate insulin-relaxin gene family and the chromosomal regions in which they reside. We analyzed the gene content surrounding the human insulin/relaxin genes with respect to what family they belonged to and if the duplication history of investigated families parallels the evolution of the insulin-relaxin fami...

Cortright, Ronald N., John L. Azevedo, Jr., Qian Zhou, Madhur Sinha, Walter J. Pories, Samar I. Itani, and G. Lynis Dohm. Protein kinase C modulates insulin action in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 278: E553–E562, 2000.—There is good evidence from cell lines and rodents that elevated protein kinase C (PKC) overexpression/activity causes insulin resistance. Therefore, ...

The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs. This extension is absent from the human insulin receptor but resembles a region in insulin receptor substrate (IRS) proteins which binds to the phosphatidylinositol (PI) 3-kinase and mediates mitogenesis. The function of a chimeric DIR cont...

Although interaction of human insulin with its receptor is studied to considerable extent such studies are currently lacking with recombinant insulin in-spite of its rampant clinical use. It is known that at molecular level the interaction of recombinant insulin with insulin receptor is similar to human insulin but not exactly same. With the increasing incidence of diabetes throughout the globe...