Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice

Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame −15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice

A single supplement of a standardised bilberry (Vaccinium myrtillus L.) extract (36 % wet weight anthocyanins) modifies glycaemic response in individuals with type 2 diabetes controlled by diet and lifestyle

Peer reviewedPublisher PD

New therapies for obesity

Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss through lifestyle changes results in modest weight loss long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in ≥ 15% weight loss and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for treatment of obesity with main target the reduction of appetite. The efficacy of semaglutide 2.4 mg/week - the latest glucagon like peptide-1 (GLP-1) receptor analogue - on weight loss for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where ≥15% weight loss is feasible. Moreover, the weight loss achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional weight loss compared to GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies. This article provides a review of the currently available interventions for weight loss and weight maintenance with a focus on pharmacological therapies for obesity approved over the last decade, as well as the emerging development of new obesity pharmacotherapies.</p