Insulin secretion in the conscious mouse is biphasic and pulsatile.

Islets in most species respond to increased glucose with biphasic insulin secretion, marked by a sharp first-phase peak and a slowly rising second phase. Mouse islets in vitro, however, lack a robust second phase. To date, this observation has not been extended in vivo.

Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice.

A portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion that results in hepatic 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophosphate (ZMP) concentrations of approximately 4 micromol/g liver increases hepatic glycogenolysis and glucose output. ZMP is an AMP analog that mimics the regulatory actions of this nucleotide. The aim of this study was to measure hepatic AMP concentrations in response to increasing energy requirements to test the hypothesis that AMP achieves concentrations during exercise, consistent with a role in stimulation of hepatic glucose metabolism.

Plasminogen activator inhibitor-1 modulates adipocyte differentiation.

Increased plasminogen activator inhibitor-1 (PAI-1) is linked to obesity and insulin resistance. However, the functional role of PAI-1 in adipocytes is unknown. This study was designed to investigate effects and underlying mechanisms of PAI-1 on glucose uptake in adipocytes and on adipocyte differentiation.

Mobilization of glucose from the liver during exercise and replenishment afterward.

The liver is anatomically well situated to regulate blood glucose. It is positioned downstream from the pancreas, which releases the key regulatory hormones glucagon and insulin. It is also just downstream from the gut, permitting efficient extraction of ingested glucose and preventing large excursions in systemic glucose after a glucose-rich meal.

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin.

This study aimed to test whether stimulation of net hepatic glucose output (NHGO) by increased concentrations of the AMP analog, 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl-5-monophosphate, can be suppressed by pharmacological insulin levels. Dogs had sampling (artery, portal vein, hepatic vein) and infusion (vena cava, portal vein) catheters and flow probes (hepatic artery, portal vein) implanted >16 days before study. Protocols consisted of equilibration (-130 to -30 min), basal (-30 to 0 min), and hyperinsulinemic-euglycemic (0-150 min) periods.

The prevalence of depression in two districts of Uganda.

Background: Little information is available on the prevalence of depression in Uganda. Given the recent political history of Uganda, depression may be common.

Method: The aim was to estimate the point prevalence of probable clinical depressive disorder among the general population in two contrasting districts of Uganda.

A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis.

Background: Erythrokeratodermia variabilis (EKV) is an autosomal dominant or recessive genodermatosis characterized by the coexistence of randomly occurring, transient, erythematous patches and hyperkeratosis of the skin. The disorder has been mapped to chromosome 1p35.1 but is genetically heterogeneous.

Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse.

Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if exercise capacity is dependent on muscle HK protein content. C57Bl/6 mice with a 50% HK knockout (HK+/-), no genetic manipulation (wild-type, WT) and an approximately 3-fold HK overexpression (HKTg) were tested.

Interaction of physiological mechanisms in control of muscle glucose uptake.

1. Control of glucose uptake is distributed between three steps. These are the rate that glucose is delivered to cells, the rate of transport into cells, and the rate that glucose is phosphorylated within these same cells.

Portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion overcomes hyperinsulinemic suppression of endogenous glucose output.

AMP-activated protein kinase (AMPK) plays a key role in regulating metabolism, serving as a metabolic master switch. The aim of this study was to assess whether increased concentrations of the AMP analog, 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophosphate, in the liver would create a metabolic response consistent with an increase in whole-body metabolic need. Dogs had sampling (artery, portal vein, hepatic vein) and infusion (vena cava, portal vein) catheters and flow probes (hepatic artery, portal vein) implanted >16 days before a study.

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside causes acute hepatic insulin resistance in vivo.

The infusion of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) causes a rise in tissue concentrations of the AMP analog 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranotide (ZMP), which mimics an elevation of cellular AMP levels. The purpose of this work was to determine the effect of raising hepatic ZMP levels on hepatic insulin action in vivo. Dogs had sampling and infusion catheters as well as flow probes implanted 16 days before an experiment.

Glucoregulation during and after exercise in health and insulin-dependent diabetes.

An elegant control system prevents hypoglycemia despite dramatic increments in glucose usage by working muscle. Insulin excess disrupts this control system, leading to hypoglycemia. Recent hypoglycemic episodes blunt the glucoregulatory response to subsequent exercise, and exercise blunts the glucoregulatory response to subsequent insulin excess.

NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease.

Objectives: The etiology and mechanism leading to granuloma formation in patients with Crohn's disease (CD) are presently unknown. The first susceptibility gene to be identified as a risk factor for CD is the NOD2/CARD15 gene on Chromosome 16. Mutations in NOD2 could affect the intracellular response to bacterial products and may eventually lead to granuloma formation.