The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation to genetic risk profiles in diabetic and nondiabetic donors. Islets from donors with T2D ex

Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have

We previously showed that dietary sphingomyelin (SM) inhibited cholesterol absorption in animals. The key enzyme hydrolyzing SM in the gut is alkaline sphingomyelinase (alk-SMase, NPP7). Here using fecal dual-isotope ratio method we compared cholesterol absorption in the wild type (WT) and alk-SMase knockout (KO) mice. The animals were fed an emulsion containing (14)C-cholesterol and (3)H-sitoster

Patients with low thyroid peroxidase antibodies (anti-TPO) and increased TSH-receptor antibodies (TRAb) at diagnosis of Graves' disease (GD) have been suggested to have an increased risk to develop Graves' ophthalmopathy (GO). The aim was to evaluate if GO development can be predicted.This is an observational study with registration of possible GD and GO risk factors.399 patients with GD were regi

The most frequently used, and effective, treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of T2D in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on ß-cell function and ß-cell mass in the pig, a species highly remini

Carboxylic acids (CAs), amino acids (AAs) and carbohydrates (CHs) in dissolved free forms can be readily assimilated by aquatic bacteria and metabolized at high growth efficiencies. Previous studies have shown that these low-molecular-weight (LMW) substrates are released by phytoplankton but also that unidentified LMW compounds of terrestrial origin is a subsidy for bacterial metabolism in unprodu

Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metform

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp32

BACKGROUND: Clinical guidelines seldom provide in depth information about the most suitable type and intensity of exercise to obtain optimal benefit in different subgroups of T2D individuals. The aim of this study was to examine the effect of group exercise training on exercise capacity, insulin sensitivity and HbA1c in women with diabetes. METHODS: Twenty-two women with T2D participated in a supe

Background: A family history of melanoma is associated with an increased risk of melanoma and probably of other, discordant cancers. Limited data are available on familial mortality in melanoma. If fatal forms of melanoma were associated with fatal forms of melanoma or of some other cancers, only studies on familial mortality rather than on familial incidence might be able to detect them. Furtherm