Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

AIMS: Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets. METHODS: Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100 mg/kg), thiazolidinedione rosiglitazone (10 mg/kg), or sulfonylurea tolbutamide (20 mg/kg) for 10 days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence. RESULTS: The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet β-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of α-cells and β-cell apoptosis with tolbutamide; increased relative number of β-cells and bi-hormonal insulin + glucagon + cells with metformin. These effects were accompanied by normalisation of food and fluid intake with only minor effects on glycaemia at the low doses of the agents employed. CONCLUSIONS: Our data suggest that metformin and rosiglitazone attenuate the depletion of the β-cell pool in the streptozotocin-induced diabetes, whereas tolbutamide exacerbates the β-cell apoptosis, but is likely to protect β-cells from chronic hyperglycaemia by directly elevating insulin secretion. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-021-01620-6

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

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