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Transient extreme insulin resistance in a critically ill patient:A case report

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World Journal of Clinical Cases 2025年第8期13卷 35-40页

作者： Xiu-Yu Wei Hsiu-Nien Shen Department of Internal Medicine Taichung Veterans General HospitalTaichung 407TaiwanChina Department of Intensive Care Medicine Chi Mei Medical CenterTainan 710TaiwanChina

BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin ***,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is *** SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of ***,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose *** Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically *** should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.

关键词： Hyperglycemia insulin insulin resistance Sepsis Critical illness Case report

Isoleucine Enriched Branched-Chain Amino Acid Supplement Improves Glucose and insulin Sensitivity in Healthy College-Age Males but Not in Females

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Food and Nutrition Sciences 2025年第1期16卷 137-152页

作者： Michael Dellogono Lyra Clark Mahdi Garelnabi Thomas A. Wilson Biomedical Engineering and Biotechnology Program University of Massachusetts Lowell Lowell MA USA Department of Biomedical and Nutritional Sciences University of Massachusetts Lowell Lowell MA USA

Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.

关键词： Isoleucine Branched-Chain Amino Acids Glucose Tolerance insulin

insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution

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World Journal of Gastroenterology 2010年第45期16卷 5693-5700页

作者： Mohamed Amine Zaouali Susagna Padrissa-Altés Ismail Ben Mosbah Hassen Ben Abdennebi Olivier Boillot Antoni Rimola Dalila Saidane-Mosbahi Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institut d'Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas08036 BarcelonaSpain Unitat de Transplantament de Fetgei Viabilitat del' Empelt Institut d'Investigacions Biomèdiques August Pii Sunyer08036 BarcelonaSpain Laboratory of Human Physiology Faculty of PharmacyUniversity of Monastir5000 MonastirTunisia Unit of Hepatic Transplantation Edouard Herriot Hospital69003 LyonFrance Biomedical Research Center Esther Koplowitz CIBER-ehdInstitute of Health Carlos Ⅲ08036 BarcelonaSpain

AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. METHODS: Steatotic livers were preserved for 24 h in IGL-1  solution supplemented with or without IGF-1 and then perfused "ex vivo " for 2 h at 37℃. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein ***: Steatotic livers preserved in IGL-1 solutionsupplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also ***: IGL-1  enrichment with IGF-1 increasedfatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.

关键词： AKT Institut georges lopez-1 solution insulin like growth factor-1 Ischemia reperfusion injury Nitric oxide Oxidative stress Steatotic graft preservation

insulin improves cardiomyocyte contractile function through enhancement of SERCA2a activity in simulated ischemia/reperfusion

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Acta Pharmacologica Sinica 2006年第7期27卷 919-926页

作者： Jie YU~2 Hai-feng ZHANG~2 Feng WU~2 Qiu-xia LI~2 Heng MA~2 Wen-yi GUO~3 Hai-chang WANG~3 Feng GAO~(2,3,4,5)2 Department of Physiology3 Department of Cardiology,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China 4 Institute of Molecular Medicine,Peking University,Beijing 100871,China Department of Physiology Xijing Hospital Fourth Military Medical University Xi'an China Department of Cardiology Xijing Hospital Fourth Military Medical University Xi'an China Institute of Molecular Medicine Peking University Beijing China

Aim:insulin exerts anti-apoptotic effects in both cardiomyocytes and coronaryendothelial cells following ischemia/reperfusion（I/R）via the Akt-endothelial ni-tric oxide synthase survival signal *** important insulin signalingmight further contribute to the improvement of cardiac function after *** this study,we tested the hypothesis that sarcoplasmic reticulum calcium-AT-Pase（SERCA2a）is involved in the insulin-induced improvement of cardiac con-tractile function following I/***:Ventricular myocytes were enzymaticallyisolated from adult SD *** I/R was induced by perfusing cells withchemical anoxic solution for 15 min followed by reperfusion with Tyrode's solu-tion with or without insulin for 30 *** shortening and intracellularcalcium transients were assessed and underlying mechanisms were ***:Reperfusion with insulin(10-7mol/L)significantly improved the recoveryof contractile function（n=15-20 myocytes from 6-8 hearts,Pinsulin-treated I/R cardiomyocytes,which were markedly inhibited by pretreatment of cells with a specific Akt ***,inhibition of Akt activity abolished insulin-induced positive contrac-tile and calcium transients responses in I/R ***:Thesedata demonstrated for the first time that insulin improves the recovery of contrac-tile function in simulated I/R cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion.

关键词： insulin ischemia/reperfusion cardiomyocyte contraction calcium transients SERCA2a Akt

insulin requirement profiles and related factors of insulin pump therapy in patients with type 2 diabetes

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Science China(Life Sciences) 2019年第11期62卷 1506-1513页

作者： Xubin Yang Hongrong Deng Xiuzhen Zhang Daizhi Yang Jinhua Yan Bin Yao Jianping Weng Wen Xu Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetologythe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Endocrinology and Metabolism Shenzhen People s HospitalShenzhen 518020China Department of Endocrinology of the First Affiliated Hospital Division of Life Sciences and Medicine of the University of Science and Technology of China(USTC)Hefei 230026China

Continuous subcutaneous insulin infusion(CSII)is an effective therapy to control hyperglycemia in both patients with type 1 diabetes and type 2 ***,there is little data investigating the insulin dose setting during CSII therapy in type 2 diabetes to achieve optimal glycemic control and avoid the risk of ***,this study is aimed to assess the dose characteristics of insulin requirement and explore the related clinical factors in patients with type 2 diabetes who were treated with CSII.A total of 327 patients(195 males)aged 52.9±12.5 years old were included in this *** were treated with CSII to achieve the target fasting capillary blood glucose(4.4-7.0 mmol L^(-1))and 2-h postprandial capillary blood glucose(4.4-10.0 mmol L^(-1))by adjusting insulin infusion according to the seven-point capillary blood glucose *** daily insulin dose(TDD),total daily insulin dose per kilogram(TDD kg-1)and the ratio of total basal insulin dose(TBD)to TDD(%TBa)were calculated after patients achieved the glucose targets for at least 3 days via 1-2 weeks of CSII *** insulin dose,insulin dosing patterns and the relevant clinical factors were *** mean ratio of basal/bolus insulin distribution of all patients was 40%:60%.Patients with central obesity needed more TDD(51.3±17.1 U versus 43.5±14.0 U,P<0.05)and TDD kg^(-1)(0.8±0.3 U kg^(-1)versus 0.7±0.2 U kg^(-1),P<0.05)than those without central ***'s correlation analysis demonstrated that TDD was positively correlated with body mass index(BMI),waist circumference(WC),baseline fasting plasma glucose(FPG),fasting C-peptide level,2 h-postprandial C-peptide level and time to achieve glycemic target(all P<0.05);TDD kg^(-1)was positively correlated with waist-to-hip ratio(WHR),baseline FPG,glycosylated hemoglobin Ale(HbAlc),fasting C-peptide level and time to achieve glycemic target,and negatively correlated with BMI(all P<0.05).Multiple linear regression analyses reveale

关键词： continuous subcutaneous insulin infusion insulin requirement profiles type 2 diabetes

insulin: a small protein with a long journey

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Protein & Cell 2010年第6期1卷 537-551页

作者： Qingxin Hua Department of Biochemistry Case Western Reserve UniversityClevelandOhio 44106-4935USA

insulin is a hormone that is essential for regulating energy storage and glucose metabolism in the *** in liver,muscle,and fat tissues stimulates the cell to take up glucose from blood and store it as glycogen in liver and *** of insulin control causes diabetes mellitus(DM).insulin is the unique medicine to treat some forms of *** population of diabetics has dramatically increased over the past two decades,due to high absorption of carbohydrates(or fats and proteins),lack of physical exercise,and development of new diagnostic *** present,the two largest developing countries(India and China)and the largest developed country(United States)represent the top three countries in terms of diabetic *** is a small protein,but contains almost all structural features typical of proteins:α-helix,β-sheet,β-turn,high order assembly,allosteric T→R-transition,and conformational changes in amyloidal *** than ten years’efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing,especially at the initial stage that forms the nascent *** structural switches are also known to regulate insulin binding to receptors and progress has been made to identify the residues involved in ***,resolving the complex structure of insulin and its receptor remains a challenge in insulin ***,the accumulated knowledge of insulin structure has allowed us to specifically design a new ultra-stable and active single-chain insulin analog(SCI-57),and provides a novel way to design super-stable,fast-acting and cheaper insulin formulations for DM *** this long journey of insulin study will benefit basic research in proteins and in pharmaceutical therapy.

关键词： insulin diabetes receptor binding folding disulfide pairing NMR

insulin and insulin mutants stimulate glucose uptake in rat adipocytes

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Science China(Life Sciences) 1999年第1期42卷 63-67页

作者：姚矢音张新堂许英镐张信娜朱尚权 1. Shanghai Institute of Biochemistry Chinese Academy of Sciences 200031 Shanghai China

A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

关键词： rat adipocytes glucose uptake insulin [B2-Lys]-insulin [B3-Lys]-insulin.

insulin affects sperm capacity in pig through nitric oxide

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Asian Journal of Andrology 2013年第6期15卷 835-837,I0011页

作者： Saveria Aquila Francesca Giordano Carmela Guido Vittoria Rago Amalia Carpino Department of Pharmacy Health Science and Nutrition University of Calabria Arcavacata di Rende Cosenza 87036 Italy Health Centre University of Calabria Arcavacata di Rende Cosenza 87036 Italy

insulin （Ins） has recently been demonstrated to have the ability to induce the capacitation process in pig spermatozoa. In various mammalian species, capacitation has been linked to the nitric oxide （NO） signalling; therefore, this study investigated NO production in Ins-treated pig spermatozoa by fluorescence-activated cell sorting. For the same samples, sperm capacitation was evaluated chlortetracycline staining, protein tyrosine phosphorylation pattern and acrosomal status. A significant increase of the intrasperm NO level and the activation of three capacitation indices were detected in response to Ins treatment. Conversely, sperm preincubation with an NO synthase inhibitor （N-nitro-L-arginine methyl ester） or with the anti-Ins receptor β （IRβ） antibody reversed all of the Ins-related effects. These results suggest that Ins has the capacity to enhance intracellular NO concentrations in pig spermatozoa and indicate a oossible NO implication upon Ins oromotion of caoacitation.

关键词： acrosome reaction insulin nitric oxide pig sperm capacitation

Synthesis and characterization of insulin-5-Fu conjugate,enabling insulin as multi-drug carrier via dendritic approach

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Chinese Chemical Letters 2007年第3期18卷 247-250页

作者： Juan Huang Jian Wei Wang Tao Gong Zhi Rong Zhang Key Laboratory of Drug Targeting Ministry of Education West China School of Pharmacy Sichuan University Chengdu 610041 China

To enable insulin as multi-drug carrier, we designed and synthesized dendritic linker molecule bearing three 5-fluorouracil residues at the branch ends. The new conjugate showed excellent water solubility. The stabilities under different conditions were investigated. The results showed that the conjugate was a potential prodrug to release free 5-Fu.

关键词： insulin 5-Fluorouracil Prodrug Characterization Stability