Diabetes最新文献_第8页

Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study. 二甲双胍对 2 型糖尿病患者周围神经形态的影响：一项横断面观察研究。

Diabetes Pub Date : 2024-11-01 DOI: 10.2337/db24-0365

Roshan Dhanapalaratnam, Tushar Issar, Leiao Leon Wang, Darren Tran, Ann M Poynten, Kerry-Lee Milner, Natalie C G Kwai, Arun V Krishnan

{"title":"Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study.","authors":"Roshan Dhanapalaratnam, Tushar Issar, Leiao Leon Wang, Darren Tran, Ann M Poynten, Kerry-Lee Milner, Natalie C G Kwai, Arun V Krishnan","doi":"10.2337/db24-0365","DOIUrl":"10.2337/db24-0365","url":null,"abstract":"Diabetic peripheral neuropathy (DPN) affects ∼50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The current study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. Participants with type 2 diabetes (n = 69) receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasonography, nerve conduction studies, and axonal excitability studies. Also concurrently screened were 318 participants who were not on metformin, and 69 were selected as disease control subjects and matched to the metformin participants for age, sex, diabetes duration, BMI, HbA1c, and use of other diabetes therapies. Medical record data over the previous 20 years were analyzed for previous metformin use. Mean tibial nerve cross-sectional area was lower in the metformin group (metformin 14.1 ± 0.7 mm2, nonmetformin 16.2 ± 0.9 mm2, P = 0.038), accompanied by reduction in neuropathy symptom severity (P = 0.021). Axonal excitability studies demonstrated superior axonal function in the metformin group, and mathematical modeling demonstrated that these improvements were mediated by changes in nodal Na+and K+conductances. Metformin treatment is associated with superior nerve structure and clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1875-1882"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PNLIPRP1 Hypermethylation in Exocrine Pancreas Links Type 2 Diabetes and Cholesterol Metabolism. 胰腺外分泌中 PNLIPRP1 的高甲基化与 2 型糖尿病和胆固醇代谢有关。

Diabetes Pub Date : 2024-11-01 DOI: 10.2337/db24-0215

Lucas Maurin, Lorella Marselli, Mathilde Boissel, Lijiao Ning, Raphael Boutry, Justine Fernandes, Mara Suleiman, Carmela De Luca, Audrey Leloire, Vincent Pascat, Bénédicte Toussaint, Souhila Amanzougarene, Mehdi Derhourhi, Anne Jörns, Sigurd Lenzen, François Pattou, Julie Kerr-Conte, Mickaël Canouil, Piero Marchetti, Amélie Bonnefond, Philippe Froguel, Amna Khamis

{"title":"PNLIPRP1 Hypermethylation in Exocrine Pancreas Links Type 2 Diabetes and Cholesterol Metabolism.","authors":"Lucas Maurin, Lorella Marselli, Mathilde Boissel, Lijiao Ning, Raphael Boutry, Justine Fernandes, Mara Suleiman, Carmela De Luca, Audrey Leloire, Vincent Pascat, Bénédicte Toussaint, Souhila Amanzougarene, Mehdi Derhourhi, Anne Jörns, Sigurd Lenzen, François Pattou, Julie Kerr-Conte, Mickaël Canouil, Piero Marchetti, Amélie Bonnefond, Philippe Froguel, Amna Khamis","doi":"10.2337/db24-0215","DOIUrl":"10.2337/db24-0215","url":null,"abstract":"We postulated that type 2 diabetes (T2D) predisposes patients to exocrine pancreatic diseases through (epi)genetic mechanisms. We explored the methylome (using MethylationEPIC arrays) of the exocrine pancreas in 141 donors, assessing the impact of T2D. An epigenome-wide association study of T2D identified hypermethylation in an enhancer of the pancreatic lipase-related protein 1 (PNLIPRP1) gene, associated with decreased PNLIPRP1 expression. PNLIPRP1 null variants (found in 191,000 participants in the UK Biobank) were associated with elevated glycemia and LDL cholesterol. Mendelian randomization using 2.5M SNP Omni arrays in 111 donors revealed that T2D was causal of PNLIPRP1 hypermethylation, which in turn was causal of LDL cholesterol. Additional AR42J rat exocrine cell analyses demonstrated that Pnliprp1 knockdown induced acinar-to-ductal metaplasia, a known prepancreatic cancer state, and increased cholesterol levels, reversible with statin. This (epi)genetic study suggests a role for PNLIPRP1 in human metabolism and exocrine pancreatic function, with potential implications for pancreatic diseases.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1908-1918"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-Intensity Interval Training, Caloric Restriction, or Their Combination Have Beneficial Effects on Metabolically Acquired Peripheral Neuropathy. 高强度间歇训练、热量限制或它们的组合对代谢获得性周围神经病变有好处。

Diabetes Pub Date : 2024-11-01 DOI: 10.2337/db23-0997

Stéphanie A Eid, Sarah E Elzinga, Bhumsoo Kim, Amy E Rumora, John M Hayes, Andrew Carter, Crystal Pacut, Adam M Allouch, Emily J Koubek, Eva L Feldman

{"title":"High-Intensity Interval Training, Caloric Restriction, or Their Combination Have Beneficial Effects on Metabolically Acquired Peripheral Neuropathy.","authors":"Stéphanie A Eid, Sarah E Elzinga, Bhumsoo Kim, Amy E Rumora, John M Hayes, Andrew Carter, Crystal Pacut, Adam M Allouch, Emily J Koubek, Eva L Feldman","doi":"10.2337/db23-0997","DOIUrl":"10.2337/db23-0997","url":null,"abstract":"Peripheral neuropathy (PN) is a prevalent and debilitating complication of obesity, prediabetes, and type 2 diabetes, which remains poorly understood and lacks disease-modifying therapies. Fortunately, diet and/or exercise have emerged as effective treatment strategies for PN. Here, we examined the impact of caloric restriction (CR) and high-intensity interval training (HIIT) interventions, alone or combined (HIIT-CR), on metabolic and PN outcomes in high-fat diet (HFD) mice. HFD feeding alone resulted in obesity, impaired glucose tolerance, and PN. Peripheral nerves isolated from these mice also developed insulin resistance (IR). CR and HIIT-CR, but not HIIT alone, improved HFD-induced metabolic dysfunction. However, all interventions improved PN to similar extents. When examining the underlying neuroprotective mechanisms in whole nerves, we found that CR and HIIT-CR activate the fuel-sensing enzyme AMPK. We then performed complimentary in vitro work in Schwann cells, the glia of peripheral nerves. Treating primary Schwann cells with the saturated fatty acid palmitate to mimic prediabetic conditions caused IR, which was reversed by the AMPK activator, AICAR. Together, these results enhance our understanding of PN pathogenesis, the differential mechanisms by which diet and exercise may improve PN, and Schwann cell-specific contributions to nerve insulin signaling and PN progression.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1895-1907"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

REDD1 Is a Promising Therapeutic Target to Combat the Development of Diabetes Complications: A Report on Research Supported by Pathway to Stop Diabetes. REDD1 是应对糖尿病并发症发展的有希望的治疗靶点：由 Pathway to Stop Diabetes 支持的研究报告。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/dbi24-0013

Siddharth Sunilkumar, Michael D Dennis

{"title":"REDD1 Is a Promising Therapeutic Target to Combat the Development of Diabetes Complications: A Report on Research Supported by Pathway to Stop Diabetes.","authors":"Siddharth Sunilkumar, Michael D Dennis","doi":"10.2337/dbi24-0013","DOIUrl":"10.2337/dbi24-0013","url":null,"abstract":"The stress response protein regulated in development and DNA damage response 1 (REDD1) has emerged as a key player in the pathogenesis of diabetes. Diabetes upregulates REDD1 in a variety of insulin-sensitive tissues, where the protein acts to inhibit signal transduction downstream of the insulin receptor. REDD1 functions as a cytosolic redox sensor that suppresses Akt/mTORC1 signaling to reduce energy expenditure in response to cellular stress. Whereas a transient increase in REDD1 contributes to an adaptive cellular response, chronically elevated REDD1 levels are implicated in disease progression. Recent studies highlight the remarkable benefits of both whole-body and tissue-specific REDD1 deletion in preclinical models of type 1 and type 2 diabetes. In particular, REDD1 is necessary for the development of glucose intolerance and the consequent rise in oxidative stress and inflammation. Here, we review studies that support a role for chronically elevated REDD1 levels in the development of diabetes complications, reflect on limitations of prior therapeutic approaches targeting REDD1 in patients, and discuss potential opportunities for future interventions to improve the lives of people living with diabetes. This article is part of a series of Perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1553-1562"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 3-Week Ketogenic Diet Increases Skeletal Muscle Insulin Sensitivity in Individuals With Obesity: A Randomized Controlled Crossover Trial. 为期三周的生酮饮食可提高肥胖症患者骨骼肌的胰岛素敏感性--随机对照交叉试验。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db24-0162

Thien Vinh Luong, Mette Glavind Bülow Pedersen, Caroline Bruun Abild, Katrine Meyer Lauritsen, Mette Louise Gram Kjærulff, Niels Møller, Lars Christian Gormsen, Esben Søndergaard

{"title":"A 3-Week Ketogenic Diet Increases Skeletal Muscle Insulin Sensitivity in Individuals With Obesity: A Randomized Controlled Crossover Trial.","authors":"Thien Vinh Luong, Mette Glavind Bülow Pedersen, Caroline Bruun Abild, Katrine Meyer Lauritsen, Mette Louise Gram Kjærulff, Niels Møller, Lars Christian Gormsen, Esben Søndergaard","doi":"10.2337/db24-0162","DOIUrl":"10.2337/db24-0162","url":null,"abstract":"A ketogenic diet (KD) can induce weight loss and improve glycemic regulation, potentially reducing the risk of type 2 diabetes development. To elucidate the underlying mechanisms behind these beneficial effects of a KD, we investigated the impact of a KD on organ-specific insulin sensitivity (IS) in skeletal muscle, liver, and adipose tissue. We hypothesized that a KD would increase IS in skeletal muscle. The study included 11 individuals with obesity who underwent a randomized, crossover trial with two 3-week interventions: 1) a KD and 2) a standard diet. Skeletal muscle IS was quantified as the increase in glucose disposal during a hyperinsulinemic-euglycemic clamp (HEC). Hepatic IS and adipose tissue IS were quantified as the relative suppression of endogenous glucose production (EGP) and the relative suppression of palmitate flux during the HEC. The KD led to a 2.2-kg weight loss and increased insulin-stimulated glucose disposal, whereas the relative suppression of EGP during the HEC was similar. In addition, the KD decreased insulin-mediated suppression of lipolysis. In conclusion, a KD increased skeletal muscle IS in individuals with obesity.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1631-1640"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The miR-203/ZBTB20/MAFA Axis Orchestrates Pancreatic β-Cell Maturation and Identity During Weaning and Diabetes. miR-203/ZBTB20/MAFA轴协调断奶和糖尿病期间胰腺β细胞的成熟和特性。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db23-0604

Yating Li, Yuqian Yang, Yi Sun, Lu He, Lin Zhao, Haoran Sun, Xiaoai Chang, Rui Liang, Shusen Wang, Xiao Han, Yunxia Zhu

{"title":"The miR-203/ZBTB20/MAFA Axis Orchestrates Pancreatic β-Cell Maturation and Identity During Weaning and Diabetes.","authors":"Yating Li, Yuqian Yang, Yi Sun, Lu He, Lin Zhao, Haoran Sun, Xiaoai Chang, Rui Liang, Shusen Wang, Xiao Han, Yunxia Zhu","doi":"10.2337/db23-0604","DOIUrl":"10.2337/db23-0604","url":null,"abstract":"Maturation of postnatal β-cells is regulated in a cell-autonomous manner, and metabolically stressed β-cells regress to an immature state, ensuring defective β-cell function and the onset of type 2 diabetes. The molecular mechanisms connecting the nutritional transition to β-cell maturation remain largely unknown. Here, we report a mature form of miRNA (miR-203)/ZBTB20/MAFA regulatory axis that mediates the β-cell maturation process. We show that the level of the mature form of miRNA (miR-203) in β-cells changes during the nutritional transition and that miR-203 inhibits β-cell maturation at the neonatal stage and under high-fat diet conditions. Using single-cell RNA sequencing, we demonstrated that miR-203 elevation promoted the transition of immature β-cells into CgBHi endocrine cells while suppressing gene expressions associated with β-cell maturation in a ZBTB20/MAFA-dependent manner. ZBTB20 is an authentic target of miR-203 and transcriptionally upregulates MAFA expression. Manipulating the miR-203/ZBTB20/MAFA axis may therefore offer a novel strategy for boosting functional β-cell numbers to alleviate diabetes.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1673-1686"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of AMPK and GAPDH by Transglutaminase 2 Plays a Pivotal Role in Microvascular Leakage in Diabetic Retinas. 转谷氨酰胺酶 2 对 AMPK 和 GAPDH 的调节在糖尿病视网膜微血管渗漏中起着关键作用。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db23-0885

Hye-Yoon Jeon, Ah-Jun Lee, Chan-Hee Moon, Kwon-Soo Ha

{"title":"Regulation of AMPK and GAPDH by Transglutaminase 2 Plays a Pivotal Role in Microvascular Leakage in Diabetic Retinas.","authors":"Hye-Yoon Jeon, Ah-Jun Lee, Chan-Hee Moon, Kwon-Soo Ha","doi":"10.2337/db23-0885","DOIUrl":"10.2337/db23-0885","url":null,"abstract":"Diabetic retinopathy is the most common microvascular complication caused by chronic hyperglycemia and is a leading cause of blindness; however, the underlying molecular mechanism has not been clearly elucidated. Therefore, we investigated whether regulation of AMPK and GAPDH by transglutaminase 2 (TGase2) is important for hyperglycemia-induced microvascular leakage in the diabetic retina. In human retinal endothelial cells (HRECs) and diabetic mouse retinas, we found that TGase2, activated by sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels, played an essential role in hyperglycemia-induced vascular leakage. ROS generation and TGsae2 activation were involved in hyperglycemia-induced AMPK dephosphorylation, which resulted in vascular endothelial-cadherin (VE-cadherin) disassembly and increased fluorescein isothiocyanate-dextran extravasation. Furthermore, high glucose-induced TGase2 activation suppressed GAPDH activity, determined by an on-chip activity assay, through inhibition of AMPK, which induced VE-cadherin disassembly and endothelial permeability in HRECs. Overall, our findings suggest that inhibition of AMPK and GAPDH by TGase2 plays a pivotal role in hyperglycemia-induced microvascular leakage in the retinas of diabetic mice.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1756-1766"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No Evidence for Persistent Enteroviral B Infection of Pancreatic Islets in Patients With Type 1 Diabetes and Prediabetes From RNA Sequencing Data. 从 RNA-Seq 数据中未发现 1 型糖尿病患者和糖尿病前期患者胰岛持续感染 B 型肠道病毒的证据。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db24-0076

Elisabetta Manduchi, Hélène C Descamps, Jonathan Schug, Tong Da, Deeksha Lahori, Hilana El-Mekkoussi, Michael R Betts, Klaus H Kaestner

{"title":"No Evidence for Persistent Enteroviral B Infection of Pancreatic Islets in Patients With Type 1 Diabetes and Prediabetes From RNA Sequencing Data.","authors":"Elisabetta Manduchi, Hélène C Descamps, Jonathan Schug, Tong Da, Deeksha Lahori, Hilana El-Mekkoussi, Michael R Betts, Klaus H Kaestner","doi":"10.2337/db24-0076","DOIUrl":"10.2337/db24-0076","url":null,"abstract":"Persistent enterovirus B infection has been proposed as an important contributor to the etiology of type 1 diabetes. We leveraged extensive bulk RNA-sequencing (RNA-seq) data from α-, β-, and exocrine cells, as well as islet single-cell RNA-seq data from the Human Pancreas Analysis Program (HPAP), to evaluate the presence of enterovirus B sequences in the pancreas of patients with type 1 diabetes and prediabetes (no diabetes but positive for autoantibodies). We examined all available HPAP data for either assay type, including donors without diabetes and with type 1 and type 2 diabetes. To assess the presence of viral reads, we analyzed all reads not mapping to the human genome with the taxonomic classification system Kraken2 and its full viral database augmented to encompass representatives for all 28 enterovirus B serotypes for which a complete genome is available. As a secondary approach, we input the same sequence reads into the STAR aligner using these 28 enterovirus B genomes as the reference. No enterovirus B sequences were detected by either approach in any of the 243 bulk RNA libraries or in any of the 79 single-cell RNA libraries. While we cannot rule out the possibility of a very-low-grade persistent enterovirus B infection in the donors analyzed, our data do not support the notion of chronic viral infection by these viruses as a major driver of type 1 diabetes.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1697-1704"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optogenetics in Pancreatic Islets: Actuators and Effects. 胰岛的光遗传学：致动器和效应

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db23-1022

Christina G Gangemi, Harald Janovjak

{"title":"Optogenetics in Pancreatic Islets: Actuators and Effects.","authors":"Christina G Gangemi, Harald Janovjak","doi":"10.2337/db23-1022","DOIUrl":"10.2337/db23-1022","url":null,"abstract":"The islets of Langerhans reside within the endocrine pancreas as highly vascularized microorgans that are responsible for the secretion of key hormones, such as insulin and glucagon. Islet function relies on a range of dynamic molecular processes that include Ca2+ waves, hormone pulses, and complex interactions between islet cell types. Dysfunction of these processes results in poor maintenance of blood glucose homeostasis and is a hallmark of diabetes. Recently, the development of optogenetic methods that rely on light-sensitive molecular actuators has allowed perturbation of islet function with near physiological spatiotemporal acuity. These actuators harness natural photoreceptor proteins and their engineered variants to manipulate mouse and human cells that are not normally light-responsive. Until recently, optogenetics in islet biology has primarily focused on controlling hormone production and secretion; however, studies on further aspects of islet function, including paracrine regulation between islet cell types and dynamics within intracellular signaling pathways, are emerging. Here, we discuss the applicability of optogenetics to islets cells and comprehensively review seminal as well as recent work on optogenetic actuators and their effects in islet function and diabetes mellitus.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1566-1582"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance. 胰岛素对胰岛素抵抗妇女和对照组妇女体内赖氨酸和α-氨基己二酸动态及氨基酸代谢物的调节。

Diabetes Pub Date : 2024-10-01 DOI: 10.2337/db23-0977

Alice Y Chang, Aneesh K Asokan, Antigoni Z Lalia, Dhananjay Sakrikar, Ian R Lanza, Xuan-Mai Petterson, K Sreekumaran Nair

{"title":"Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance.","authors":"Alice Y Chang, Aneesh K Asokan, Antigoni Z Lalia, Dhananjay Sakrikar, Ian R Lanza, Xuan-Mai Petterson, K Sreekumaran Nair","doi":"10.2337/db23-0977","DOIUrl":"10.2337/db23-0977","url":null,"abstract":"Insulin is a key regulator of amino acid metabolism. Many plasma amino acids, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance (IR). In 18 overweight women with IR and polycystic ovary syndrome compared with 12 lean control women, high physiological insulin during a euglycemic clamp failed to normalize many elevated amino acid metabolites, including branched-chain and aromatic amino acids, α-aminobutyric acid, and lysine, but normalized α-AA. To understand the underpinnings of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared with control participants, we developed a kinetic model using [α-15N1]-lysine and [13C1]-α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in the IR and control groups but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal amino acids and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1592-1604"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141539098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0