Atypical presentation of multiple evanescent white dot syndrome involving granular lesions of varying size.

Purpose: To report an atypical presentation of multiple evanescent white dot syndrome (MEWDS).

Design: Observational case report.

Methods: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS.

Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance.

The mechanism by which increased central adiposity causes hepatic insulin resistance is unclear. The "portal hypothesis" implicates increased lipolytic activity in the visceral fat and therefore increased delivery of free fatty acids (FFA) to the liver, ultimately leading to liver insulin resistance. To test the portal hypothesis at the transcriptional level, we studied expression of several genes involved in glucose and lipid metabolism in the fat-fed dog model with visceral adiposity vs.

Mechanism of action in dogs of slow-acting insulin analog O346.

We compared metabolic effects as well as plasma and interstitial fluid kinetics of fatty acid-acylated insulin, Lys(B29)(N(epsilon)-omega-carboxynonadecanoyl)-des(B30) human insulin (O346), with previously determined kinetics of native insulin and insulin detemir. Euglycemic clamps with iv injection of O346 (90 pmol/kg) or saline control were performed in 10 male mongrel dogs under inhalant anesthesia. The t(1/2) for the clearance of O346 from plasma was 375.

Elevated glucagon-like peptide-1-(7-36)-amide, but not glucose, associated with hyperinsulinemic compensation for fat feeding.

We previously developed a canine model of central obesity and insulin resistance by supplementing the normal chow diet with 2 g cooked bacon grease/kg body weight. Dogs fed this fatty diet maintained glucose tolerance with compensatory hyperinsulinemia. The signal(s) responsible for this up-regulation of plasma insulin is unknown.

Albumin binding of acylated insulin (NN304) does not deter action to stimulate glucose uptake.

NN304 [Lys(B29)-tetradecanoyl des(B30) human insulin] is a potentially therapeutic insulin analog designed to exhibit protracted glucose-lowering action. In dogs with infusion rates similar to insulin itself, NN304 exhibits similar glucose uptake (R(d)) stimulation with delayed onset of action. This compartmental modeling study was to determine if NN304 action could be accounted for by the approximately 2% unbound NN304 concentration.

Mode of transcapillary transport of insulin and insulin analog NN304 in dog hindlimb: evidence for passive diffusion.

A defect in transcapillary transport of insulin in skeletal muscle and adipose tissue has been proposed to play a role in the insulin resistance that leads to type 2 diabetes, yet the mechanism of insulin transfer across the capillary endothelium from plasma to interstitium continues to be debated. This study examined in vivo the interstitial appearance of insulin in hindlimb using the fatty acid acylated insulin analog Lys(B29)-tetradecanoyl des-(B30) human insulin, or NN304, as a marker for insulin transport. If the insulin transport were a saturable process, then "swamping" the capillary endothelial insulin receptors with native insulin would suppress the subsequent appearance in interstitial fluid of the insulin analog NN304.