Ileal brake: neuropeptidergic control of intestinal transit.

Digestion and absorption of a meal are time-intensive processes. To optimize digestion and absorption, transit of the meal through the gastrointestinal tract is regulated by a complex integration of neuropeptidergic signals generated as the jejunal brake and ileal brake response to nutrients. Mediators involved in the slowing of transit responses include peptide YY (PYY), chemosensitive afferent neurons, intestinofugal nerves, noradrenergic nerves, myenteric serotonergic neurons, and opioid neurons.

Management of small intestinal bacterial overgrowth.

Similar to that of all mammals, the human gastrointestinal tract is colonized by 100 trillion bacteria shortly after birth. Remarkably, in the open-tube arrangement of the intestine, this bacterial population is tightly compartmentalized to the distal gut. Contamination of the small intestine with colonic bacterial flora or small intestinal bacterial overgrowth (SIBO) has been understood previously as a complication of uncommon conditions associated with obvious intestinal stasis.

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.

Primacy of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog.

Obesity is highly correlated with insulin resistance and the development of type 2 diabetes. Insulin resistance will result in a decrease in insulin's ability to stimulate glucose uptake into peripheral tissue and will suppress glucose production by the liver. However, the development of peripheral and hepatic insulin resistance relative to one another in the context of obesity-associated insulin resistance is not well understood.

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.

Extreme insulin resistance of the central adipose depot in vivo.

Despite the well-described association between obesity and insulin resistance, the physiologic mechanisms that link these two states are poorly understood. The present study was performed to elucidate the role of visceral adipose tissue in whole-body glucose homeostasis. Dogs made abdominally obese with a moderately elevated fat diet had catheters placed into the superior mesenteric artery so that the visceral adipose bed could be insulinized discretely.