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The Insulin Response to Oral Glucose in GIP and GLP-1 Receptor Knockout Mice : Review of the Literature and Stepwise Glucose Dose Response Studies in Female Mice

A key factor for the insulin response to oral glucose is the pro-glucagon derived incretin hormone glucagon-like peptide-1 (GLP-1), together with the companion incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). Studies in GIP and GLP-1 receptor knockout (KO) mice have been undertaken in several studies to examine this role of the incretin hormones. In the present study, we revie

Activation of human γδ T cells and NK cells by Staphylococcal enterotoxins requires both monocytes and conventional T cells

Staphylococcal enterotoxins (SE) pose a great threat to human health due to their ability to bypass antigen presentation and activate large amounts of conventional T cells resulting in a cytokine storm potentially leading to toxic shock syndrome. Unconventional T- and NK cells are also activated by SE but the mechanisms remain poorly understood. In this study, the authors aimed to explore the unde

Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965

SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compound C/ Dorsomorphin. Here, we studied the effects of SBI-0206965 on AMPK signalling and metabolic readouts in multiple cell types, including hepa

Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test

Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a

Glucose-lowering action through targeting islet dysfunction in type 2 diabetes : Focus on dipeptidyl peptidase-4 inhibition

Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglyce

Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials

Aims: To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contribu

A plasmodium cysteine protease required for efficient transition from the liver infection stage

The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood

JUP/plakoglobin is regulated by salt-inducible kinase 2, and is required for insulin-induced signalling and glucose uptake in adipocytes

BACKGROUND: Salt-inducible kinase 2 (SIK2) is abundant in adipocytes, but downregulated in adipose tissue from individuals with obesity and insulin resistance. Moreover, SIK isoforms are required for normal insulin signalling and glucose uptake in adipocytes, but the underlying molecular mechanisms are currently not known. The adherens junction protein JUP, also termed plakoglobin or γ-catenin, ha

Immunocyte single cell analysis of vaccine-induced narcolepsy

Increased incidence of narcolepsy type 1 (NT1) was observed following Pandemrix®‐vaccination, initiated as a preventive measure against the 2009 Influenza pandemic. Here, single cell analysis was conducted to suggest a lower number of CD8+CD27+ T cells among these patients. These findings provide understanding into the autoimmune pathogenesis of NT1.

NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis

Sterile liver inflammation and fibrosis are associated with many liver disorders of different etiologies. Both type 1 and type 2 inflammatory responses have been reported to contribute to liver pathology. However, the mechanisms controlling the balance between these responses are largely unknown. Natural killer T (NKT) cells can be activated to rapidly secrete cytokines and chemokines associated w

Glucose effectiveness : Lessons from studies on insulin-independent glucose clearance in mice

Besides insulin-mediated transport of glucose into the cells, an important role is also played by the non-insulin-mediated transport. This latter process is called glucose effectiveness (acronym SG), which is estimated by modeling of glucose and insulin data after an intravenous glucose administration, and accounts for ≈70% of glucose disposal. This review summarizes studies on SG, mainly in human

Five-year follow-up of new cases after a coeliac disease mass screening

OBJECTIVE: We previously performed a population-based mass screening of coeliac disease in children aged 12 years in two birth cohorts resulting in 296 seropositive children, of whom 242 were diagnosed with coeliac disease after duodenal biopsies. In this follow-up study, we wanted to identify new cases in the screening population that tested negative-either converting from potential coeliac disea

The Glucose Sensitivity of Insulin Secretion-Lessons from In Vivo and In Vitro Studies in Mice

This study explored the relationship between the glucose dose and insulin response from beta cells in vivo and in vitro in mice. Glucose was administered intravenously at different dose levels (from 0 to 0.75 g/kg) in anesthetized C57BL/6J mice, and the glucose and insulin concentrations were determined in samples taken after 50 min. Furthermore, freshly isolated mouse islets were incubated for 60

Assessing the Effect of Incretin Hormones and Other Insulin Secretagogues on Pancreatic Beta-Cell Function : Review on Mathematical Modelling Approaches

Mathematical modelling in glucose metabolism has proven very useful for different reasons. Several models have allowed deeper understanding of the relevant physiological and pathophysiological aspects and promoted new experimental activity to reach increased knowledge of the biological and physiological systems of interest. Glucose metabolism modelling has also proven useful to identify the parame

Hydrogen sulfide potentiates the protective effects of nitrite against myocardial ischemia-reperfusion injury in type 2 diabetic rats

Decreased heart levels of nitric oxide (NO) and hydrogen sulfide (H2S) in type 2 diabetes (T2D) are associated with a higher risk of mortality following ischemia-reperfusion (IR) injury. This study aimed to determine the effects of co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on IR injury in the isolated heart from rats with T2D. Two-month-old male rats were divided into 5 gr

Investigating photomultiplier tube nonlinearities in high-speed phosphor thermometry using light emitting diode simulated decay curves

Photomultiplier tube (PMT) nonlinearities relevant for single shot high-speed lifetime phosphor thermometry were investigated by simulating decay curves with a light emitting diode (LED) at repetition rates between 1 Hz and 10 kHz. The PMT gain, LED decay time, and background radiant flux were also varied to investigate their impact on the measured decay time error. Errors in the measured decay tiPhotomultiplier tube (PMT) nonlinearities relevant for single shot high-speed lifetime phosphor thermometry were investigated by simulating decay curves with a light emitting diode (LED) at repetition rates between 1 Hz and 10 kHz. The PMT gain, LED decay time, and background radiant flux were also varied to investigate their impact on the measured decay time error. Errors in the measured decay ti

β cell function and insulin resistance have gender-specific correlations with carotid intima-media thickness in type 2 diabetes

ObjectiveThe relationships between carotid intima-media thickness (C-IMT) and β cell function and insulin resistance in patients with type 2 diabetes (T2D) have not been fully elucidated. This study is to investigate whether impaired glucose metabolism is etiologically associated with C-IMT in patients with T2D.MethodsThe study group consisted of 490 (284 men, 206 women) participants. Venous blood

Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped

Aims/hypothesis: The rapid remission of type 2 diabetes by a diet very low in energy correlates with a marked improvement in glucose-stimulated insulin secretion (GSIS), emphasising the role of beta cell dysfunction in the early stages of the disease. In search of novel mechanisms of beta cell dysfunction after long-term exposure to mild to severe glucotoxic conditions, we extensively characterise