journal
https://read.qxmd.com/read/38640066/do-we-need-a-new-hypothesis-for-katp-closure-in-%C3%AE-cells-distinguishing-the-baby-from-the-bathwater
#1
JOURNAL ARTICLE
Leslie Sherwin Satin, Jeremías Corradi, Arthur Stewart Sherman
No abstract text is available yet for this article.
April 19, 2024: Diabetes
https://read.qxmd.com/read/38608284/the-early-pathogenesis-of-diabetic-retinopathy-and-its-attenuation-by-sodium-glucose-transporter-2-inhibitors
#2
JOURNAL ARTICLE
Mayumi Yamato, Nao Kato, Ken-Ichi Yamada, Toyoshi Inoguchi
The early pathogenetic mechanism of diabetic retinopathy (DR) and its treatment remain unclear. Therefore, we investigated the early pathogenic alterations in DR using streptozotocin-induced diabetic mice and the protective effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors against these alterations. Retinal vascular leakage was assessed by dextran fluorescence angiography. Retinal thickness and vascular leakage were increased 2 and 4 weeks after onset of diabetes, respectively. Immunostaining showed that morphological change of microglia (amoeboid form) was observed at 2 weeks...
April 12, 2024: Diabetes
https://read.qxmd.com/read/38608276/depletion-of-tbc1d4-improves-the-metabolic-exercise-response-by-overcoming-genetically-induced-peripheral-insulin-resistance
#3
JOURNAL ARTICLE
Christian Springer, Christian Binsch, Deborah Weide, Laura Toska, Anna Lena Cremer, Heiko Backes, Anna K Scheel, Lena Espelage, Jörg Kotzka, Sebastian Sill, Anette Kurowski, Daebin Kim, Sandra Karpinski, Theresia M Schnurr, Torben Hansen, Sonja Hartwig, Stefan Lehr, Sandra Cames, Jens Brüning, Matthias Lienhard, Ralf Herwig, Stefan Börno, Bernd Timmermann, Hadi Al-Hasani, Alexandra Chadt
The RabGTPase-activating protein (RabGAP) TBC1D4 (=AS160) represents a key component in the regulation of glucose transport into skeletal muscle and white adipose tissue (WAT) and is therefore crucial during the development of insulin resistance and type-2 diabetes. Increased daily activity has been shown to be associated with improved postprandial hyperglycemia in allele carriers of a loss-of-function variant in the human TBC1D4 gene. Using conventional Tbc1d4-deficient mice (D4KO) fed a high-fat diet (HFD), we show that already a moderate endurance exercise training leads to substantially improved glucose and insulin tolerance and enhanced expression levels of markers for mitochondrial activity and browning in WAT from D4KO animals...
April 12, 2024: Diabetes
https://read.qxmd.com/read/38608261/pharmacological-activation-of-pdc-flux-reverses-lipid-induced-inhibition-of-insulin-action-in-muscle-during-recovery-from-exercise
#4
JOURNAL ARTICLE
Christian S Carl, Marie M Jensen, Kim A Sjøberg, Dumitru Constantin-Teodosiu, Ian R Hill, Rasmus Kjøbsted, Paul L Greenhaff, Jørgen F P Wojtaszewski, Erik A Richter, Andreas M Fritzen, Bente Kiens
Insulin resistance is a risk factor for type 2 diabetes and exercise can improve insulin sensitivity. However, following exercise high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a cross-over design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemiceuglycemic clamp five hours after one-legged exercise with: 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC-activator, dichloroacetate (DCA)...
April 12, 2024: Diabetes
https://read.qxmd.com/read/38608241/engineering-a-pathway-to-glucose-responsive-therapeutics
#5
REVIEW
Matthew J Webber
In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes® Program. Pathway took a multifaceted approach to provide key funding to diabetes researchers in advancing a broad spectrum of research programs centered on all aspects of understanding, managing, and treating diabetes. Herein the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes...
April 11, 2024: Diabetes
https://read.qxmd.com/read/38603470/efficient-vascular-and-neural-engraftment-of-stem-cell-derived-islets
#6
JOURNAL ARTICLE
Julia Thorngren, Anja Brboric, Svitlana Vasylovska, Daisy Hjelmqvist, Gunilla T Westermark, Jonna Saarimäki-Vire, Jouni Kvist, Diego Balboa, Timo Otonkoski, Per-Ola Carlsson, Joey Lau
Pluripotent stem cell-derived islets (SC-islets) now emerge as a new source for beta-cell replacement therapy. While the function of human islet transplants is hampered by excessive cell death post-transplantation, contributing factors include inflammatory reactions, insufficient revascularization and islet amyloid formation, there is a gap in knowledge on the engraftment process of the SC-islets. In this experimental study, we investigated the engraftment capability of SC-islets at three months post-transplantation, and observed that the cell apoptosis rates were lower, but the vascular density was similar in SC-islets to that of human islets...
April 11, 2024: Diabetes
https://read.qxmd.com/read/38602922/genetic-subtypes-of-prediabetes-healthy-lifestyle-and-risk-of-type-2-diabetes
#7
JOURNAL ARTICLE
Yang Li, Guo-Chong Chen, Jee-Young Moon, Rhonda Arthur, Daniela Sotres-Alvarez, Martha L Daviglus, Amber Pirzada, Josiemer Mattei, Krista M Perreira, Jerome I Rotter, Kent D Taylor, Yii-Der Ida Chen, Sylvia Wassertheil-Smoller, Tao Wang, Thomas E Rohan, Joel D Kaufman, Robert Kaplan, Qibin Qi
Prediabetes is a heterogenous metabolic state with various risk for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic whites without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n=3,677) and UKBB (n=16,284) separately, based on these pPRSs...
April 11, 2024: Diabetes
https://read.qxmd.com/read/38602880/engineering-a-pathway-to-glucose-responsive-therapeutics
#8
REVIEW
Matthew J Webber
In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes® Program. Pathway took a multifaceted approach to provide key funding to diabetes researchers in advancing a broad spectrum of research programs centered on all aspects of understanding, managing, and treating diabetes. Herein the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes...
April 11, 2024: Diabetes
https://read.qxmd.com/read/38593250/comment-on-pataky-et-al-divergent-skeletal-muscle-metabolomic-signatures-of-different-exercise-training-modes-independently-predict-cardiometabolic-risk-factors-diabetes-2024-73-23-37
#9
JOURNAL ARTICLE
https://read.qxmd.com/read/38551899/role-of-cardiorespiratory-fitness-and-mitochondrial-oxidative-capacity-in-reduced-walk-speed-of-older-adults-with-diabetes
#10
JOURNAL ARTICLE
Sofhia V Ramos, Giovanna Distefano, Li-Yung Lui, Peggy M Cawthon, Philip Kramer, Ian J Sipula, Fiona M Bello, Theresa Mau, Michael J Jurczak, Anthony J Molina, Erin E Kershaw, David J Marcinek, Eric Shankland, Frederico G S Toledo, Anne B Newman, Russell T Hepple, Stephen B Kritchevsky, Bret H Goodpaster, Steven R Cummings, Paul M Coen
Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults. The impact of cardiorespiratory fitness and mitochondrial oxidative capacity on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes as well as determine their relative contribution to slower walking speed in older adults with diabetes...
March 29, 2024: Diabetes
https://read.qxmd.com/read/38530928/genetic-evidence-for-distinct-biological-mechanisms-that-link-adiposity-to-type-2-diabetes-towards-precision-medicine
#11
JOURNAL ARTICLE
Angela Abraham, Madeleine Cule, Marjola Thanaj, Nicolas Basty, M Amin Hashemloo, Elena P Sorokin, Brandon Whitcher, Stephen Burgess, Jimmy D Bell, Naveed Sattar, E Louise Thomas, Hanieh Yaghootkar
We aimed to unravel the mechanisms connecting adiposity to type 2 diabetes. We employed MR-Clust to cluster independent genetic variants associated with body fat percentage (388 variants) and BMI (540 variants) based on their impact on type 2 diabetes. We identified five clusters of adiposity-increasing alleles associated with higher type 2 diabetes risk (unfavorable adiposity) and three clusters associated with lower risk (favorable adiposity). We then characterized each cluster based on various biomarkers, metabolites and Magnetic Resonance Imaging-based measures of fat distribution and muscle quality...
March 26, 2024: Diabetes
https://read.qxmd.com/read/38530923/epistasis-between-hla-drb1-16-02-01-and-slc16a11-t-c-g-t-t-reduces-odds-for-type-2-diabetes-in-southwest-american-indians
#12
JOURNAL ARTICLE
Robert C Williams, Robert L Hanson, Bjoern Peters, Kendall Kearns, William C Knowler, Clifton Bogardus, Leslie J Baier
We sought to identify genetic/immunologic contributors of type 2 diabetes in an indigenous American community by genotyping all study participants for both high resolution HLA-DRB1 alleles and SLC16A11 to test their risk and/or protection for T2D. These genes were selected based on independent reports that HLA-DRB1*16:02:01 is protective for T2D and that SLC16A11 associates with T2D in individuals with BMI<35kg/m2, and here test the interaction of the two loci with a more complete dataset and perform a BMI sensitivity test...
March 26, 2024: Diabetes
https://read.qxmd.com/read/38530908/adiponectin-reduces-glomerular-endothelial-glycocalyx-disruption-and-restores-glomerular-barrier-function-in-a-mouse-model-of-type-2-diabetes
#13
JOURNAL ARTICLE
Sarah Fawaz, Aldara Martin Alonso, Yan Qiu, Raina Ramnath, Holly Stowell-Connolly, Monica Gamez, Carl May, Colin Down, Richard J Coward, Matthew J Butler, Gavin I Welsh, Simon C Satchell, Rebecca R Foster
Adiponectin has vascular anti-inflammatory and protective effects. Whilst adiponectin is known to protect against the development of albuminuria, historically the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnC). In diabetes, eGlx dysfunction occurs before podocyte damage, hence we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD)...
March 26, 2024: Diabetes
https://read.qxmd.com/read/38512770/effect-of-dapagliflozin-on-renal-and-hepatic-glucose-kinetics-in-t2dm-and-ngt-subjects
#14
JOURNAL ARTICLE
Xi Chen, Devjit Tripathy, Robert Chilton, Andrea Hansis-Diarte, Marzieh Salehi, Carolina Solis-Herrera, Eugenio Cersosimo, Ralph A DeFronzo
Acute and chronic SGLT-2 inhibition increase endogenous glucose production (EGP). However, the organ - liver versus kidney - responsible for the increase in EGP has not been identified. 20 T2DM and 12 NGT subjects received [3-3H]-glucose infusion (to measure total EGP) in combination with arterial and renal vein catheterization and PAH infusion for determination of renal blood flow. Total EGP, net renal arteriovenous balance, and renal glucose production were measured before and 4 hours after dapagliflozin and placebo administration...
March 21, 2024: Diabetes
https://read.qxmd.com/read/38506957/response-to-comment-letter-muscle-metabolomics-and-exercise-effects-on-cardiometabolic-risk
#15
JOURNAL ARTICLE
Mark W Pataky, K Sreekumaran Nair
We appreciate Dr. Astrada's interest in our recent article (1). Although he raised concern around using BMI as a screening parameter for our study, BMI was not the only "defining parameter" screening criteria in our study. Fasting glucose > 110mg/dL was also a critical exclusion criterion for the study which limits variation in metabolic characteristics in our study cohort. These and other criteria for participation in the study were reported in the original manuscript (2) from which the samples in our current study (1) were obtained...
March 20, 2024: Diabetes
https://read.qxmd.com/read/38506952/comparison-of-beta-cell-function-and-insulin-sensitivity-between-normal-weight-and-obese-chinese-with-young-onset-type-2-diabetes
#16
JOURNAL ARTICLE
Yingnan Fan, Elaine Chow, Cadmon K P Lim, Yong Hou, Sandra T F Tsoi, Baoqi Fan, Eric S H Lau, Alice P S Kong, Ronald C W Ma, Hongjiang Wu, Juliana C N Chan, Andrea O Y Luk
Normal-weight individuals with usual-onset type 2 diabetes had reduced beta-cell function and greater insulin sensitivity compared to their obese counterparts. The relative contribution of beta-cell dysfunction and insulin resistance to young-onset type 2 diabetes (YOD) among normal-weight individuals is not well established. In 44 individuals with YOD (24 normal-weight and 20 obese) and 24 healthy controls with normoglycemia (12 normal-weight and 12 obese), we conducted 2-h 12mmol/L hyperglycemic clamps to measure acute (0-10 minute) and steady-state (100-120 minute) insulin and C-peptide responses, and insulin sensitivity index...
March 20, 2024: Diabetes
https://read.qxmd.com/read/38506804/cpt1a-protects-podocytes-from-lipotoxicity-and-apoptosis-in-vitro-and-alleviates-diabetic-nephropathy-in-vivo
#17
JOURNAL ARTICLE
Yajuan Xie, Qian Yuan, Ben Tang, Yaru Xie, Yiling Cao, Yang Qiu, Jieyu Zeng, Zhiwen Wang, Hua Su, Chun Zhang
Defective fatty acid oxidation (FAO) has been implicated in diabetic kidney disease (DKD), yet little is known about the role of carnitine palmitoyltransferase-1A (CPT1A), a pivotal rate-limiting enzyme of FAO, in the progression of DKD. Here, we investigate whether CPT1A is a reliable therapeutic target for DKD. We first confirmed the downregulation expression of CPT1A in glomeruli from diabetic patients. We further evaluated the function of CPT1A in diabetic models. Overexpression of CPT1A exhibited protective effects in diabetic conditions, improving albuminuria and glomerular sclerosis, as well as mitigating glomerular lipid deposits and podocyte injury in streptozotocin-induced diabetic mice...
March 20, 2024: Diabetes
https://read.qxmd.com/read/38502858/intermittent-fasting-improves-glucose-homeostasis-not-entirely-dependent-on-caloric-restriction-in-db-db-male-mice
#18
JOURNAL ARTICLE
Dinghao Zheng, Xiaosi Hong, Xiaodan He, Jianghong Lin, Shujin Fan, Jinli Wu, Zhuoxian Liang, Sifan Chen, Li Yan, Meng Ren, Wei Wang
Intermittent fasting (IF), which involves prolonged fasting intervals accompanied by caloric restriction, is an effective dietary treatment for obesity and diabetes. Although IF offers many benefits, it is difficult to determine whether these benefits are the consequences of caloric restriction. Every-other-day feeding (EODF) is a commonly used IF research model. This study was designed to identify other effectors of EODF, in addition to caloric restriction, and the possible underlying mechanisms. Diabetic db/db mice were divided into three groups: ad libitum (AL), meal-feeding (MF) and EODF...
March 19, 2024: Diabetes
https://read.qxmd.com/read/38502790/metabolic-fluxes-in-the-renal-cortex-are-dysregulated-in-vivo-in-response-to-high-fat-diet
#19
JOURNAL ARTICLE
Clinton M Hasenour, Deveena R Banerjee, Jamey D Young
Diabetes and obesity are risk factors for kidney disease. While renal glucose production increases in diabetes, recent data suggest that gluconeogenic and oxidative capacity decline in kidney disease. Thus, metabolic dysregulation caused by diet-induced insulin resistance may sensitize the kidney for a loss in function. Here we examined how diet-induced insulin resistance disrupts mitochondrial metabolic fluxes in the renal cortex in vivo. C57Bl/6J mice were rendered insulin resistant through high-fat (HF) feeding; anaplerotic, cataplerotic, and oxidative metabolic fluxes in the cortex were quantified through 13C-isotope tracing during a hyperinsulinemic-euglycemic clamp...
March 19, 2024: Diabetes
https://read.qxmd.com/read/38498375/genetic-evidence-of-causal-relation-between-intestinal-glucose-absorption-and-early-postprandial-glucose-response-a-mendelian-randomization-study
#20
JOURNAL ARTICLE
Simon Peschard, Violeta Raverdy, Pierre Bauvin, Rebecca Goutchtat, Veronique Touche, Bruno Derudas, Celine Gheeraert, Julie Dubois-Chevalier, Robert Caiazzo, Gregory Baud, Camille Marciniak, Helene Verkindt, Naima Oukhouya Daoud, Carel W Le Roux, Philippe Lefebvre, Bart Staels, Sophie Lestavel, François Pattou
The post-prandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose-co-transporter-1 (SGLT1). This study utilizes Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1547 subjects with class II/III obesity from the ABOS cohort, the study employs SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression...
March 18, 2024: Diabetes
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