The success of pancreatic β-cells transplantation to treat type 1 diabetes has been hindered by massive β-cell dysfunction and loss that follows the procedure. Hypoxia-mediated cell death considered one main difficulties must be overcome for regarded as a reliable therapy. Here we have investigated mechanisms underlying in response hypoxia (1% O2). Our studies show mouse insulinoma line 6 (Min6) cells undergo apoptosis with caspase-3 activation occurring early 2 h following exposure hypoxia....

Abstract Diabetes is known to increase susceptibility infections, partly due impaired granulocyte function and changes in the innate immunity. Here, we investigate effect of diabetes, high glucose on expression antimicrobial peptide, psoriasin putative consequences for E. coli urinary tract infection. Blood, urine, urine exfoliated cells from patients are studied. The influence insulin examined during hyperglycemic clamps individuals with prediabetes euglycemic hyperinsulinemic clamped type...

To investigate the association between fruit and vegetable intake (FVI) risk of developing prediabetes type 2 diabetes (T2D) in a Swedish prospective cohort study.Subjects were 6961 men women aged 35-56 years old at baseline, participating Stockholm Diabetes Prevention Program cohort. By design, was enriched by 50% with subjects that had family history diabetes. Anthropometric measurements, oral glucose tolerance tests questionnaires on lifestyle dietary factors carried out baseline two...

Previous and present evidence ascribes an important role to overstimulation of beta-cells for the secretory abnormalities associated with type 2 diabetes. The abnormality most clearly linked is elevated ratio circulating proinsulin insulin. Evidence obtained in human pancreatic islets suggests that aberrations insulin oscillations occur diabetes could at least part be cytoplasmic Ca2+ induced by overstimulation. Furthermore, a transplantation model, we have long-lasting, perhaps...

Accumulation of lipids in non-adipose tissues is often associated with Type 2 diabetes and its complications. Elevated expression the lipogenic transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), has been demonstrated islets liver diabetic animals. To elucidate molecular mechanisms underlying SREBP-1c-induced औ-cell dysfunction, we employed Tet-On inducible system to achieve tightly controlled conditional nuclear active form SREBP-1c (naSREBP-1c) INS-1 cells....

Abstract Aims To compare outcomes of glucagon‐stimulated C‐peptide tests (GSCTs) in people with latent autoimmune diabetes adults (LADA) after a 21‐month intervention either insulin or the dipeptidyl peptidase‐4 inhibitor sitagliptin. Research design and methods We included 64 glutamic acid decarboxylase (GAD) antibody‐positive individuals, who were diagnosed <3 years before study, aged 30 to 70 years, without clinical need for treatment. stratified participants by age body mass index...

Objective Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed characterize such effects test for pharmacological means alleviate a negative impact Methods Design Rat human were subjected 5.5 h hypoxia after which viability parameters measured subsequent the hypoxic period and/or following 22 re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during prior Results Insulin contents decreased 23% 61%...

We investigated the impact of a diabetic state with hyperglycemia on morphometry β cell mitochondria and modifying influence K+-ATP channel opener we related in vivo findings glucose effects vitro. For experiments islets from syngeneic rats were transplanted under kidney capsule to neonatally streptozotocin-diabetic or non-diabetic recipients. Diabetic recipients received vehicle, tifenazoxide (NN414), intragastrically for 9 weeks. Non-diabetic vehicle. Transplants excised 7 d after...

Relative hypersecretion of proinsulin is a feature type 2 diabetes. We investigated to what extent this can be induced in human pancreatic islets by elevated glucose or fatty acids, two major abnormalities the diabetic state. A 48-h culture period with 27 mmol/l increased intraislet proinsulin-to-insulin (PI/I) ratio 5.0-fold, owing preferential decrease insulin. The PI/I medium was enhanced 1.9-fold versus cultured 5.5 glucose. This effect persisted after normalization levels: during 60-min...

Sustained hyperglycemia desensitizes pancreatic B-cells to glucose. Infusion of diazoxide protects against this effect, i.e. an insulin response glucose is preserved after exposure the drug in vivo. The mechanisms behind aftereffect were presently investigated vitro. In one type experiment, rat islets exposed (75 micrograms/ml) for 20-22 h tissue culture. Previous increased 2.4-fold 16.7 mM final batch-type incubations. This effect was not altered by adding (10 mU/ml) culture medium. other...

Toll-like receptors (TLRs) have been implicated in the pathogenesis of type 2 diabetes. We examined function TLR3 glucose metabolism and diabetes–related phenotypes animals humans. is highly expressed pancreas, suggesting that it can influence metabolism. Using a diet-induced obesity model, we show TLR3-deficient mice had enhanced glycemic control, facilitated by elevated insulin secretion. Despite having high levels, Tlr3−/− did not experience disturbances whole-body sensitivity, they...

Objective To study the effect of induced hypoglycaemia on fetal wellbeing as indicated by heart rate and umbilical artery flow velocity waveforms. Design A prospective experimental investigation. Setting High risk pregnancy unit diabetes research at Karolinska Institutet, Danderyd Hospital, a university affiliated hospital. Participants Ten women with insulin‐dependent mellitus in third trimester pregnancy. Interventions The rate, blood waveforms maternal catecholamine levels were...

SUMMARY A method is described for the quantitative bioassay of melanocytestimulating hormone (MSH) activity using skin lizard Anolis carolinensis in vitro . The colour changes were registered photoelectrically as reflexion green monochromatic light. Synthetic α-MSH (CIBA-Geigy Ltd) was used standard. can detect MSH at a concentration down to 0·01–0·05 ng α-MSH/ml, and allows detection normal rat plasma. mean precision assay λ about 0·13. This thus combines high sensitivity with good...

Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca(2+)-activated monovalent cation is involved in stimulus-secretion coupling mouse pancreatic β-cells. We studied role of TRPM5 channel regulating insulin secretion and cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) rat β-cells by using triphenylphosphine oxide, selective inhibitor channel.Insulin from islets Sprague-Dawley rats was measured batch incubations. Cytoplasmic...

Objective To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Methods Design Insulin-producing INS-1 832/13 cells were exposed to 18 hours hypoxia followed by 20–22 re-oxygenation. Mitochondrial was measured high-resolution respirometry both intact permeabilized cells, latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins complexes (Western blotting),...

Objective To study the effect of induced hypoglycaemia on serum levels placental hormones oestriol, human lactogen, growth hormone and progesterone in third trimester pregnancy. Design A prospective experimental investigation. Setting High risk pregnancy unit diabetes research at Karolinska Institutet Danderyd Hospital, a university hospital. Participants Ten women with insulin‐dependent mellitus Methods Venous blood samples were collected every 15 minutes for analyses progesterone, lactogen...

Prolonged periods of "beta-cell rest" exert beneficial effects on insulin secretion from pancreatic islets subjected to a high-glucose environment. Here, we tested for short-term intermittent rest achieved by diazoxide. Rat were cultured 48 h with 27 mmol/l glucose alone, diazoxide present 2 every 12 or continuous 48-h presence Both protocols enhanced the postculture response glucose, 200 mumol/l tolbutamide, and 20 KCl. Intermittent did not affect islet content only K(ATP)-dependent...

We assessed bronchial reactivity to increasing doses of inhaled methacholine (MCH) in a population-based study on alpha1-antitrypsin. compared 34 consecutive 48- 50-yr-old heterozygous (Pi-MZ) men with 31 the same age normal Pi phenotype (Pi-M) matched for smoking habits. There was no significant difference between control FEV1 or MCH Pi-MZ and Pi-M group. Twelve subjects 11 showed fall greater than equal 15% (PC 15%). Smokers increased sensitivity both groups, although there nonsmoking...

The pancreatic β-cells respond to an increased glycolytic flux by secreting insulin. signal propagation goes via mitochondrial metabolism, which relays the different routes. One route is ATP production that, ATP-sensitive K + (K ) channels, modulates cell membrane potential allow calcium influx, triggers insulin secretion. There also at least one other “amplifying” whose nature debated; possible candidates are cytosolic NADPH or malonyl-CoA production. We have used mathematical modeling...