Search PubMed⌕ Search

Biomedical subjects

H Lewis

Publications and source records attributed to H Lewis.

187 records · Page 11Linked to original sources
PubMedDate not supplied

Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.

Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), there is no direct evidence to conclusively implicate this receptor in the regulation of mammalian glucose homeostasis. Here we report two different heterozygous mutations in the ligand-binding domain of PPARgamma in three subjects with severe insulin resistance. In the PPARgamma crystal structure, the mutations destabilize helix 12 which mediates transactivation. Consistent with this, both receptor mutants are markedly transcriptionally impaired and, moreover, are able to inhibit the action of coexpressed wild-type PPARgamma in a dominant negative manner. In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age. Our findings represent the first germline loss-of-function mutations in PPARgamma and provide compelling genetic evidence that this receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man.

Adult↗
PubMedDate not supplied

[Furosemide-amiloride combination in the treatment of ascitic-edema in patients with hepatic cirrhosis].

The combination of furosemide-amiloride was used in the management of fluid retention in 16 cirrhotic patients. The study lasted 60 days. In 15 out of the 16 patients a clinical response was observed, namely increased urinary volumen and reduction of abdominal girth. The body weight was reduced by a mean of 7.7 Kg. Serum potassium rose, within normal limits, in 14 patients and a reduction of urinary potassium elimination was observed. Mild hepatic encephalopathy was noticeable in 3 cases, rapidly responding to treatment reduction or withdrawal. The combination of furosemide-amiloride seems to be of value in the management of fluid retention in liver cirrhosis and is uncommonly associated to side effects.

Adult↗