908 research outputs found
An update on peptide-based therapies for type 2 diabetes and obesity
Long-acting analogues of the naturally occurring incretin, glucagon-like peptide-1 (GLP-1) and those modified to interact also with receptors for glucose-dependent insulinotropic polypeptide (GIP) have shown high glucose-lowering and weight-lowering efficacy when administered by once-weekly subcutaneous injection. These analogues herald an exciting new era in peptide-based therapy for type 2 diabetes (T2D) and obesity. Of note is the GLP-1R agonist semaglutide, available in oral and injectable formulations and in clinical trials combined with the long-acting amylin analogue, cagrilintide. Particularly high efficacy in both glucose- and weight lowering capacities has also been observed with the GLP-1R/GIP-R unimolecular dual agonist, tirzepatide. In addition, a number of long-acting unimolecular GLP-1R/GCGR dual agonist peptides and GLP-1R/GCGR/GIPR triagonist peptides have entered clinical trials. Other pharmacological approaches to chronic weight management include the human monoclonal antibody, bimagrumab which blocks activin type II receptors and is associated with growth of skeletal muscle, an antibody blocking activation of GIPR to which are conjugated GLP-1R peptide agonists (AMG-133), and the melanocortin-4 receptor agonist, setmelanotide for use in certain inherited obesity conditions. The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
A microfabricated sensor for thin dielectric layers
We describe a sensor for the measurement of thin dielectric layers capable of
operation in a variety of environments. The sensor is obtained by
microfabricating a capacitor with interleaved aluminum fingers, exposed to the
dielectric to be measured. In particular, the device can measure thin layers of
solid frozen from a liquid or gaseous medium. Sensitivity to single atomic
layers is achievable in many configurations and, by utilizing fast, high
sensitivity capacitance read out in a feedback system onto environmental
parameters, coatings of few layers can be dynamically maintained. We discuss
the design, read out and calibration of several versions of the device
optimized in different ways. We specifically dwell on the case in which
atomically thin solid xenon layers are grown and stabilized, in cryogenic
conditions, from a liquid xenon bath
Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice
Electrofusion-derived BRIN-BD11 cells are glucosesensitive
insulin-secreting cells which provide an
archetypal bioengineered surrogate β-cell for
insulin replacement therapy in diabetes mellitus,
5x106 BRIN-BD11 cells were implanted intraperitoneally
into severely hyperglycaemic (>24mmol/l)
streptozotocin-induced insulin-treated diabetic
athymic nude (nu/nu) mice. The implants reduced
hyperglycaemia such that insulin injections were
discontinued by 5–16 days (<17mmol/l) and normoglycaemia
(<9mmol/l) was achieved by 7–20
days. Implanted cells were removed after 28 days
and re-established in culture. After re-culture for 20
days, glucose-stimulated (16.7mmol/l) insulin
release was enhanced by 121% (p<0.001) compared
to non-implanted cells. Insulin responses to
glucagon-like peptide-1 (10−9mol/l), cholecystokinin-8 (10−8 mol/l) and L-alanine (10 mmol/l) were
increased by 32%, 31% and 68% respectively
(p<0.05–0.01). Insulin content of the cells was 148%
greater at 20 days after re-culture than before
implantation (p<0.001), but basal insulin release (at
5.6 mmol/l glucose) was not changed. After re-culture
for 40 days, insulin content declined to 68% of
the content before implantation (p<0.01), although
basal insulin release was unchanged. However, the
insulin secretory responses to glucose, glucagonlike
peptide-1, cholecystokinin-8 and L-alanine
were decreased after 40 days of re-culture to 65%,
72%, 73% and 42% respectively of the values before
implantation (p<0.05–0.01). The functional
enhancement of electrofusion-derived surrogate β-cells that were re-cultured for 20 days after implantation
and restoration of normoglycaemia indicates
that the in vivo environment could greatly assist β-cell engineering approaches to therapy for diabetes
Adsorption of Superplasticizers on Model Powders: Temperature dependance, effect on Zeta Potential and Role of Chemical Structure
Obesity: A Biobehavioral Point of View
Excerpt: If you ask an overweight person, “Why are you fat?’, you will, almost invariably, get the answer, “Because 1 eat too much.” You will get this answer in spite of the fact that of thirteen studies, six find no significant differences in the caloric intake of obese versus nonobese subjects, five report that the obese eat significantly less than the nonobese, and only two report that they eat significantly more
Recent advances in peptide-based therapies for obesity and type 2 diabetes
Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by the results of several large clinical trials with incretin-based peptide therapies. Most of these studies have been conducted with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection and once daily tablet, and the once weekly injected dual agonist tirzepatide, which interacts with receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In individuals with T2DM these therapies have achieved reductions of glycated haemoglobin (HbA1c) by >2% and lowered body weight by >10%. In some studies, these agents tested in non-diabetic, obese individuals at much higher doses have lowered body weight by >15%. Emerging evidence suggests these agents can also offer cardio-protective and potentially reno-protective effects. Other incretin-based peptide therapies in early clinical development, notably a triple GLP-1/GIP/glucagon receptor agonist (retatrutide) and a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), have shown strong efficacy. Although incretin therapies can incur adverse gastrointestinal effects these are for most patients mild-to-moderate and transient but result in cessation of treatment in some cases. Thus, the efficacy of new incretin-based peptide therapies is enhancing the opportunity to control body weight and blood glucose and improve the treatment of T2DM and obesity. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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