High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets.

Background: Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia.

Objective: To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets.

Modest hyperglycemia prevents interstitial dispersion of insulin in skeletal muscle.

Unlabelled: Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake, but this is blocked in insulin resistance. As glucotoxicity is associated with endothelial dysfunction, the observed hyperglycemia in diet-induced obese dogs may inhibit insulin access to muscle cells, and exacerbate insulin resistance. Here we asked whether interstitial insulin diffusion is reduced in modest hyperglycemia, similar to that induced by a high fat diet.

Increase in visceral fat per se does not induce insulin resistance in the canine model.

Objectives: To determine whether a selective increase of visceral adipose tissue content will result in insulin resistance.

Methods: Sympathetic denervation of the omental fat was performed under general inhalant anesthesia by injecting 6-hydroxydopamine in the omental fat of lean mongrel dogs (n = 11). In the conscious animal, whole-body insulin sensitivity was assessed by the minimal model (SI ) and the euglycemic hyperinsulinemic clamp (SICLAMP ).

Simplified method to isolate highly pure canine pancreatic islets.

Objectives: The canine model has been used extensively to improve the human pancreatic islet isolation technique. At the functional level, dog islets show high similarity to human islets and thus can be a helpful tool for islet research. We describe and compare 2 manual isolation methods, M1 (initial) and M2 (modified), and analyze the variables associated with the outcomes, including islet yield, purity, and glucose-stimulated insulin secretion (GSIS).

Diet-induced obesity prevents interstitial dispersion of insulin in skeletal muscle.

Objective: Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake.

Novel canine models of obese prediabetes and mild type 2 diabetes.

Human type 2 diabetes mellitus (T2DM) is often characterized by obesity-associated insulin resistance (IR) and beta-cell function deficiency. Development of relevant large animal models to study T2DM is important and timely, because most existing models have dramatic reductions in pancreatic function and no associated obesity and IR, features that resemble more T1DM than T2DM. Our goal was to create a canine model of T2DM in which obesity-associated IR occurs first, followed by moderate reduction in beta-cell function, leading to mild diabetes or impaired glucose tolerance.

Experimental hyperlipidemia dramatically reduces access of insulin to canine skeletal muscle.

A complex sequence of steps is required for insulin to cause glucose uptake. Impairment of any one of these steps can contribute to insulin resistance. We observed the effect of insulin resistance induced by hyperlipidemia on the dynamics of insulin injected into skeletal muscle.

Greater omentectomy improves insulin sensitivity in nonobese dogs.

Visceral adiposity is strongly associated with insulin resistance; however, little evidence directly demonstrates that visceral fat per se impairs insulin action. Here, we examine the effects of the surgical removal of the greater omentum and its occupying visceral fat, an omentectomy (OM), on insulin sensitivity (S(I)) and beta-cell function in nonobese dogs. Thirteen male mongrel dogs were used in this research study; animals were randomly assigned to surgical treatment with either OM (n = 7), or sham-surgery (SHAM) (n = 6).

Beta-cell "rest" accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model.

During insulin resistance, glucose homeostasis is maintained by an increase in plasma insulin via increased secretion and/or decreased first-pass hepatic insulin extraction. However, the relative importance of insulin secretion vs. clearance to compensate for insulin resistance in obesity has yet to be determined.

Investigation of the effect of acepromazine on intravenous glucose tolerance tests in dogs.

Objective: To investigate the effects of administration of acepromazine on IV glucose tolerance tests (IVGTTs) in dogs.

Animals: 8 male mixed-breed dogs.

Procedure: With a 1-week interval between tests, each dog underwent (in random order) an IVGTT with or without pretest administration of acepromazine maleate (0.

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.