Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog.

Objective: Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions.

Methods: Metabolic assessment was performed in healthy dogs (n = 90).

OGTT-derived measures of insulin sensitivity are confounded by factors other than insulin sensitivity itself.

Insulin resistance is an important risk factor for diabetes and other diseases. It has been important to estimate insulin resistance in epidemiological and genetic studies involving significant number of individuals. Complex and invasive protocols are impractical.

Deconvolution as a novel approach to analyze moment-to-moment free fatty acid release.

Objective: Recent studies have shown that free fatty acid (FFA) release is pulsatile and that this pattern is controlled by the sympathetic nervous system. It is, then, necessary to understand and characterize adipose tissue lipolysis to elucidate its effect on metabolism. In this study, we introduce deconvolution as a method to detect and quantify pulsatile FFA release.

Exogenously imposed postprandial-like rises in systemic glucose and GLP-1 do not produce an incretin effect, suggesting an indirect mechanism of GLP-1 action.

The insulinotropic intestinal hormone GLP-1 is thought to exert one of its effects by direct action on the pancreatic beta-cell receptors. GLP-1 is rapidly degraded in plasma, such that only a small amount of the active form reaches the pancreas, making it questionable whether this amount is sufficient to produce a direct incretin effect. The aim of our study was to assess, in a dog model, the putative incretin action of GLP-1 acting directly on the beta-cell in the context of postprandial rises in GLP-1 and glucose.

Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: a placebo-controlled study of olanzapine and risperidone in dogs.

Atypical antipsychotics have been linked to weight gain, hyperglycemia, and diabetes. We examined the effects of atypical antipsychotics olanzapine (OLZ) and risperidone (RIS) versus placebo on adiposity, insulin sensitivity (S(I)), and pancreatic beta-cell compensation. Dogs were fed ad libitum and given OLZ (15 mg/day; n = 10), RIS (5 mg/day; n = 10), or gelatin capsules (n = 6) for 4-6 weeks.

Physiological hyperinsulinemia in dogs augments access of macromolecules to insulin-sensitive tissues.

Pharmacological doses of insulin increase limb blood flow and enhance tissue recruitment for small solutes such as glucose. We investigated whether elevating insulin within the physiological range (68 +/- 6 vs. 425 +/- 27 pmol/l) can influence tissue recruitment of [(14)C]inulin, an inert diffusionary marker of molecular weight similar to that of insulin itself.

Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes.

Aims/hypothesis: Since insulin secretion in response to exogenous gastric inhibitory polypeptide (GIP) is diminished not only in patients with type 2 diabetes, but also in their normal glucose-tolerant first-degree relatives, it was the aim to investigate the integrity of the entero-insular axis in such subjects.

Methods: Sixteen first-degree relatives of patients with type 2 diabetes (4 male, 12 female, age 50+/-12 years, BMI 26.1+/-3.

Burst-like control of lipolysis by the sympathetic nervous system in vivo.

Rapid oscillations of visceral lipolysis have been reported. To examine the putative role of the CNS in oscillatory lipolysis, we tested the effects of beta(3)-blockade on pulsatile release of FFAs. Arterial blood samples were drawn at 1-minute intervals for 120 minutes from fasted, conscious dogs (n = 7) during the infusion of saline or bupranolol (1.