[Gut microbiota may have influence on glucose and lipid metabolism].

New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.

GLP-1 amidation efficiency along the length of the intestine in mice, rats and pigs and in GLP-1 secreting cell lines.

XXX: Measurements of plasma concentrations of the incretin hormone GLP-1 are complex because of extensive molecular heterogeneity. This is partly due to a varying and incompletely known degree of C-terminal amidation. Given that virtually all GLP-1 assays rely on a C-terminal antibody, it is essential to know whether or not the molecule one wants to measure is amidated.

Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia.

Background And Aims: Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia.

Materials And Methods: We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies.

Targeting the intestinal L-cell for obesity and type 2 diabetes treatment.

Degradation-resistant glucagon-like peptide-1 (GLP-1) mimetics and GLP-1 enhancers (inhibitors of dipeptidyl peptidase-4, the enzyme which degrades and inactivates GLP-1) have been used for treatment of type 2 diabetes mellitus since 2005-2006. Cutting-edge research is now focusing on uncovering the secretory mechanisms of the GLP-1-producing cells (L-cells) with the purpose of developing agonists that enhance endogenous hormone secretion. Since GLP-1 co-localizes with other anorectic peptides, cholecystokinin, oxyntomodulin/glicentin and peptide YY, L-cell targeting might cause release of several hormones at the same time, providing additive effects on appetite and glucose regulation.

Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males.

The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion.

Copenhagen study of overweight patients with coronary artery disease undergoing low energy diet or interval training: the randomized CUT-IT trial protocol.

Background: Coronary artery disease (CAD) is accountable for more than 7 million deaths each year according to the World Health Organization (WHO). In a European population 80% of patients diagnosed with CAD are overweight and 31% are obese. Physical inactivity and overweight are major risk factors in CAD, thus central strategies in secondary prevention are increased physical activity and weight loss.

Normal physical activity obliterates the deleterious effects of a high-caloric intake.

A high-caloric intake combined with a sedentary lifestyle is an important player in the development of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine if the level of physical activity has impact on the metabolic effects of a high-caloric (+2,000 kcal/day) intake. Therefore, healthy individuals on a high-caloric intake were randomized to either 10,000 or 1,500 steps/day for 14 days.

Enteroendocrine secretion of gut hormones in diabetes, obesity and after bariatric surgery.

Gastric bypass surgery is associated with a major weight loss and often causes remission in patients with type 2 diabetes. Surgery is also associated with dramatic increases in the secretion of the gut hormones, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), both of which regulate appetite and food intake, while GLP-1 in addition functions as an incretin hormone, stimulating insulin secretion. It has been possible to probe the role of GLP-1 for the diabetes resolution after gastric bypass using a GLP-1 receptor antagonist, and it is clear that the enhanced beta cell sensitivity to glucose which underlies the enhanced insulin secretion in the patients after the operation depends critically on the increased GLP-1 secretion.

Impact of the reconstruction method on delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy: a prospective randomized study.

Background: Delayed gastric emptying (DGE) is of considerable concern in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prolonged hospital stay, increased cost, and decreased quality of life add on to interventions needed to treat DGE. This study was conducted to determine if performing duodenojejunostomy via the antecolic rather than the retrocolic route improved incidence of DGE.

Appetite regulation in overweight, sedentary men after different amounts of endurance exercise: a randomized controlled trial.

Weight loss induced by endurance exercise is often disappointing, possibly due to an increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial, and postexercise appetite regulation after an intervention prescribing two amounts of endurance exercise. Sixty-four sedentary, overweight, healthy young men were randomized to control (CON), moderate-dose (MOD: ≈ 30 min/day), or high-dose (HIGH: ≈ 60 min/day) endurance exercise for 12 wk.

Distal gastrectomy in pancreaticoduodenectomy is associated with accelerated gastric emptying, enhanced postprandial release of GLP-1, and improved insulin sensitivity.

Objective: This study aims to investigate the relationship between gastric emptying, postprandial GLP-1 and insulin sensitivity after pancreaticoduodenectomy (PD).

Background: Abnormal glucose regulation is highly prevalent in patients with pancreatic neoplasm and resolves in some after PD, the cause of which is unclear. The procedure is carried out with pylorus preservation (PPPD) or with distal gastrectomy (Whipple procedure).

Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women.

OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs. This parallel intervention study investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals.

Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

Background: Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown.

Methods: We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.

Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus: a randomized cross-over trial.

Introduction: The incidence of severe hypoglycemia in type 1 diabetes has not decreased over the past decades. New treatment modalities minimizing the risk of hypoglycemic episodes and attenuating hypoglycemic cognitive dysfunction are needed. We studied if treatment with the neuroprotective hormone erythropoietin (EPO) enhances cognitive function during hypoglycemia.

Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men.

Introduction: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown.

Subjects And Methods: Twelve healthy young males were examined in a randomized, controlled, double-blinded, single-day, crossover trial to evaluate the effects of 2 hours GLP-1 infusion on kidney functions.

Is there a place for incretin therapies in obesity and prediabetes?

Incretin-based therapies exploit the insulinotropic actions of the gut hormones gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) for the treatment of diabetes and include GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4), the enzyme that inactivates the incretin hormones in the body. Both drug classes improve metabolic control in type 2 diabetes (T2DM), with GLP-1 receptor agonists also lowering body weight. Pharmacotherapy using DPP-4 inhibitors has few side effects and is weight neutral.

Regulation of urea synthesis during the acute-phase response in rats.

The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats.

Relationships among tonic and episodic aspects of motivation to eat, gut peptides, and weight before and after bariatric surgery.

Background: The interaction between motivation to eat, eating behavior traits, and gut peptides after Roux-en-Y gastric bypass (RYGB) surgery is not fully understood.

Methods: Appetite and hormone responses to a fixed liquid preload were assessed in 12 obese (body mass index 45 ± 1.9 kg/m(2)) participants immediately before and 3 days, 2 months, and 1 year after RYGB surgery.

Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis.

Background: Glucagon-like peptide-2 (GLP-2) has been suggested for the treatment of mucositis, but the peptide has also been shown to accentuate colonic dysplasia in carcinogen-treated mice. Recently, an effect on intestinal growth was discovered for glucagon-like peptide-1 (GLP-1), OBJECTIVE: To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis.

Methods: Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle.

Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice.

Introduction: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel from the intestinal endocrine cells after nutrient intake. GLP-1 is an incretin hormone and analogues are available for the treatment of type 2 diabetes mellitus (T2DM). GLP-2 is an intestinal growth hormone and is shown to promote growth of colonic adenomas in carcinogen treated mice.

Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia.

Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males.

Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine.

Purpose: Gastrointestinal mucositis is an unwanted and often dose-limiting side effect to most cancer treatments. Glucagon-like peptide-2 (GLP-2) is a peptide secreted from intestinal L-cells in response to nutrient intake. The peptide is involved in the regulation of apoptosis and proliferation in the intestine.

The L-α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in L-arginine-induced insulin release.

GPRC6A is a seven-transmembrane receptor activated by a wide range of L-α-amino acids, most potently by L-arginine and other basic amino acids. The receptor is broadly expressed, but its exact physiological role remains to be elucidated. It is well established that L-arginine stimulates insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism.

Alcohol intake and its effect on some appetite-regulating hormones in man: influence of gastroprotection with sucralfate.

Background: Alcohol stimulates appetite. Ghrelin, obestatin, glucagon-like peptide 1 and leptin are putative mediators.

Objective: We studied whether alcohol ingestion affects serum levels of these peripheral hormones, and if gastroprotective sucralfate prevents such an effect.