Viorica Ionut

Cedars-Sinai Medical Center · Department of Biomedical Sciences

Background: Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. Objective: We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. Design and methods: After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ...

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 insulin...

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. We have previously shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Th...

The hepato-portal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon- like peptide-1 (GLP-1). We have previously reported that activation of hepato-portal sensors by intraportal infusion of glucose and GLP-1, or by subcutaneous administration of GLP-1-receptor activator exenati...

A major issue of in the treatment of diabetes is the risk of hypoglycemia. Hypoglycemia is detected both centrally and peripherally in the porto-hepatic area. The portal locus for hypoglycemic detection was originally described using the "local irrigation of the liver" approach in a canine model. Further work using portal vein denervation in a rode...

BACKGROUND: Several lines of evidence show that abdominal fat is strongly associated with insulin resistance and dysglycemia (impaired glucose tolerance - IGT or type 2 diabetes mellitus - T2DM). However, which component of abdominal fat, subcutaneous or intra-abdominal, has a major impact on the development of insulin resistance and dysglycemia is...

BACKGROUND: Several lines of evidence show that abdominal fat is strongly associated with insulin resistance and dysglycemia (impaired glucose tolerance - IGT or type 2 diabetes mellitus - T2DM). However, which component of abdominal fat, subcutaneous or intra-abdominal, has a major impact on the development of insulin resistance and dysglycemia is...

Accurate quantification of insulin resistance is essential for determining efficacy of treatments to reduce diabetes risk. Gold standard methods to assess resistance are available (e.g. hyperinsulinemic clamp or minimal model), but surrogate indices based solely on fasting values have attractive simplicity. One such surrogate, the Homeostatic Model...

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, non-stimulated conditions. Metabolic assessment was performed in healthy dogs (n=90)....

Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on wei...

Glucokinase (GCK) acts as a component of the "glucose sensor" in pancreatic β-cells and possibly in other tissues, including the brain. However, >99% of GCK in the body is located in the liver, where it serves as a "gatekeeper", determining the rate of hepatic glucose phosphorylation. Mutations in GCK are a cause of maturity-onset diabetes of the y...

The endocannabinoid system is highly implicated in the development of insulin resistance associated with obesity. It has been shown that antagonism of the CB(1) receptor improves insulin sensitivity (S(I)). However, it is unknown whether this improvement is due to the direct effect of CB(1) blockade on peripheral tissues or secondary to decreased f...

Obesity has increased alarmingly in the United States and is increasing in many countries of the world. Because obesity is an important risk factor for type 2 diabetes and other chronic diseases, it is important to develop approaches to counter the rapid increase in adiposity. One approach is bariatric surgery, the most successful clinical interven...

Adipocyte size plays a key role in the development of insulin resistance. We examined longitudinal changes in adipocyte size and distribution in visceral (VIS) and subcutaneous (SQ) fat during obesity-induced insulin resistance and after treatment with CB-1 receptor antagonist, rimonabant (RIM) in canines. We also examined whether adipocyte size an...

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 wit...

Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or bot...

The full impact of the liver, through both glucose production and uptake, on systemic glucose appearance cannot be readily studied in a classical glucose clamp because hepatic glucose metabolism is regulated not only by portal insulin and glucose levels but also portal glucose delivery (the portal signal). In the present study, we modified the clas...

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...

We investigated whether rimonabant, a type 1 cannabinoid receptor antagonist, reduces visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in dogs maintained on a hypercaloric high-fat diet (HHFD). To determine whether energy expenditure contributed to body weight changes, we also calculated resting metabolic rate. Twenty male dogs r...

OBJECTIVE— Recent progress suggests that exenatide, a mimetic of glucagon-like peptide-1 (GLP-1), might lower glycemia independent of increased β-cell response or reduced gastrointestinal motility. We aimed to investigate whether exenatide stimulates glucose turnover directly in insulin-responsive tissues dependent or independent of insulinemia. RE...

Exenatide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic used in the treatment of type 2 diabetes. There is increasing evidence that GLP-1 can influence glycemia not only via pancreatic (insulinotropic and glucagon suppression) and gastric-emptying effects, but also via an independent mechanism mediated by portal vein receptors. The aim o...

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...

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 o...

Glucagon-like peptide 1 (GLP-1), an intestinal hormone released in response to a meal, is involved in glucose homeostasis via inhibition of gastric emptying and intestinal motility, increasing insulin secretion, and, possibly, via insulin-independent effects on glucose turnover. This latter effect appears to be mediated by receptors situated in the...

Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone released from the gut in response to nutrients. Besides its well-established direct effect on pancreatic beta cells, GLP-1 may also act by activating sensors in the hepatoportal area. We therefore studied the impact of putative GLP-1 sensors in the splanchnic circulation. We infused GLP-1...

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 =...

Understanding how insulin resistance develops βcell compensation is essential for understanding the development of IGT and Type 2 diabetes. Comparing different models of insulin resistance can help understand the secretion/sensitivity interaction. Treatment with the Highly Active Antiretroviral Therapy (HAART) can cause insulin resistance accompani...

It is generally accepted that glucagon-like peptide-1 (GLP-1,) an insulinotropic peptide released from the intestinal L-cells in response to a meal, acts via specific GLP-1 receptors in pancreas, in the presence of a postprandial rise in systemic glucose. However, most GLP-1 released from the intestine is inactivated before it reaches the β-cells,...

To investigate the effects of administration of acepromazine on IV glucose tolerance tests (IVGTTs) in dogs. 8 male mixed-breed dogs. With a 1-week interval between tests, each dog underwent (in random order) an IVGTT with or without pretest administration of acepromazine maleate (0.1 mg/kg, SC, 30 minutes prior to the start of the IVGTT). Food was...