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1.
Am J Health Syst Pharm ; 79(7): 547-555, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-34957477

RESUMO

PURPOSE: High-dose insulin/euglycemia (HDIE) is targeted therapy for ß-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. METHODS: Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher's exact tests. RESULTS: During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. CONCLUSION: Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.


Assuntos
Hiperinsulinismo , Hipoglicemia , Antagonistas Adrenérgicos beta , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hiperinsulinismo/induzido quimicamente , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Insulina
2.
Drug Deliv ; 29(1): 2831-2845, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36050870

RESUMO

The lipophilicity of a peptide drug can be considerably increased by hydrophobic ion pairing with amphiphilic counterions for successful incorporation into lipid-based formulations. Herein, to enhance the oral absorption of insulin (INS), a self-microemulsifying drug delivery system (SMEDDS) formulation was developed. Prior to optimization, INS was complexed with sodium n-octadecyl sulfate (SOS) to increase the loading into the SMEDDS. The INS-SOS complex was characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and its dissociation behavior. The SMEDDS was optimized using a D-optimal mixture design with three independent variables including Capmul MCM (X1, 9.31%), Labrasol (X2, 49.77%), and Tetraglycol (X3, 40.92%) and three response variables including droplet size (Y1, 115.2 nm), INS stability (Y2, 46.75%), and INS leakage (Y3, 17.67%). The desirability function was 0.766, indicating excellent agreement between the predicted and experimental values. The stability of INS-SOS against gastrointestinal enzymes was noticeably improved in the SMEDDS, and the majority of INS remained in oil droplets during release. Following oral administration in diabetic rats, the optimized SMEDDS resulted in pharmacological availabilities of 3.23% (50 IU/kg) and 2.13% (100 IU/kg). Thus, the optimized SMEDDS is a good candidate for the practical development of oral delivery of peptide drugs such as INS.


Assuntos
Diabetes Mellitus Experimental , Insulina , Administração Oral , Animais , Disponibilidade Biológica , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Ratos , Solubilidade
3.
J Cell Biol ; 221(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36053215

RESUMO

Insulin levels are essential for the maintenance of glucose homeostasis, and deviations lead to pathoglycemia or diabetes. However, the metabolic mechanism controlling insulin quantity and quality is poorly understood. In pancreatic ß cells, insulin homeostasis and release are tightly governed by insulin secretory granule (ISG) trafficking, but the required regulators and mechanisms are largely unknown. Here, we identified that VAMP4 controlled the insulin levels in response to glucose challenge. VAMP4 deficiency led to increased blood insulin levels and hyperresponsiveness to glucose. In ß cells, VAMP4 is packaged into immature ISGs (iISGs) at trans-Golgi networks and subsequently resorted to clathrin-coated vesicles during granule maturation. VAMP4-positive iISGs and resorted vesicles then fuse with lysosomes facilitated by a SNARE complex consisting of VAMP4, STX7, STX8, and VTI1B, which ensures the breakdown of excess (pro)insulin and obsolete materials and thus maintenance of intracellular insulin homeostasis. Thus, VAMP4 is a key factor regulating the insulin levels and a potential target for the treatment of diabetes.


Assuntos
Insulina , Lisossomos , Proteínas R-SNARE , Vesículas Secretórias , Diabetes Mellitus , Glucose/metabolismo , Humanos , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Lisossomos/metabolismo , Proteínas R-SNARE/metabolismo , Vesículas Secretórias/metabolismo , Rede trans-Golgi/metabolismo
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(3): 207-211, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36062786

RESUMO

Objective: To investigate the effects of continuing exercise and load-bearing interval exercise on skeletal muscle tissue cell morphology, Ras-related proteins 5 (Rab5) mRNA and protein expression and glucose metabolism in skeletal muscle of type 2 diabetic mellitus (T2DM) rats. Methods: Eight SD rats were selected as controls group (CR), the others SD rats were fed with high fat and high sugar diet for 6 weeks before injecting STZ (35 mg/kg) to construct the T2DM model. Twenty-four T2DM rats were randomly devided into T2DM model group (DRM), continuing exercise group (DCRE) and load-bearing interval exercise group (DWRE), 8 rats in each group. DCRE exercise protocol, that was 15 m/min (10 min), 20 m/min (40 min), 15 m/min (10 min), during the first 1~2 weeks, and 18 m/min (10 min), 25 m/min (40 min), 15 m/min (10 min), during the second 3~8 weeks. DWRE exercise protocol: load weight 15% / 1~2 weeks, 30% / 3~4 weeks, 45% / 5~8 weeks, with 15 m/min (5 min), 12 groups and 3 min rest between groups. After 8 weeks, pathological and morphological changes of skeletal muscle were observed by HE. Rab5 and Glucose transporte 4 (GLUT4) mRNA expressions of skeletal muscle were tested by qRT-PCR. Rab5 protein expression in skeletal muscle was tested by immunofluorescence histochemistry and Western blot, and plasma Rab5 and Glycosylated Hemoglobin (GHb) concentrations were detected by ELISA. Results: Comparison with CR, DRM showed pathological damage of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all decreased in skeletal muscle (P<0.01), the serum levels of Rab5 and GHb were both significantly elevated (P<0.01). Comparison with DRM, both DCRE and DWRE significantly improved pathological damages of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all increased in skeletal muscle (P< 0.05, P<0.01), the serum levels of Rab5 and GHb were decreased (P<0.05, P<0.01), and there was no statistical difference between DCRE and DWRE groups (P>0.05). Conclusion: Two exercise modes can improve the pathological injury of skeletal muscle in type 2 diabetic rats, and enhance GLUT4 transport capacity by improving the expression of Rab5 gene and protein in skeletal muscle, and alleviate the imbalance of glucose metabolism homeostasis in skeletal muscle. However, there was no significant difference between the effects of two exercise modes on Rab5 protein and glucose metabolism in skeletal muscle.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Músculo Esquelético , Condicionamento Físico Animal , Proteínas rab5 de Ligação ao GTP , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hemoglobina A Glicada , Insulina , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas rab5 de Ligação ao GTP/metabolismo
5.
PLoS One ; 17(9): e0273792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36067170

RESUMO

There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animais , Cães , Frutosamina , Humanos , Insulina , Insulina Regular Humana , Projetos Piloto , RNA Ribossômico 16S
6.
Cell Rep ; 40(10): 111271, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36070700

RESUMO

Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Insulina/metabolismo , Masculino , Proteômica , Qualidade de Vida , Receptores de N-Metil-D-Aspartato/metabolismo , Serina/metabolismo
7.
Comput Math Methods Med ; 2022: 8553539, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072767

RESUMO

Background: Cerebral hemorrhage, also known as hemorrhagic stroke, is a common clinical cerebrovascular disease, accounting for about 10%-30% of stroke, with high morbidity and mortality. Objective: To observe the effect of optimal management of hyperglycemia and intensive nursing on blood glucose control level and complications in patients with postoperative cerebral hemorrhage. Methods: One hundred and eight patients with postoperative cerebral hemorrhage comorbid with stress hyperglycemia admitted to our neurosurgery department from February 2019 to February 2022 were selected and divided into a general group of 54 cases and an optimized group of 54 cases by simple random method. The general group was managed with conventional care, while the optimized group developed optimized management of hyperglycemia for intensive care. The indexes related to blood glucose control, electrolytes, National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, and time to achieve blood glucose standard, insulin pumping time, patient satisfaction, and prognosis were compared between the two groups. Results: Before intervention, there was no statistical significance in the comparison of blood glucose control-related indicators and electrolytes between the two groups (P > 0.05). After 7 d and 14 d of intervention, the fasting blood glucose and 2 h postprandial blood glucose in the two groups were lower than before, while K+ and Na+ were higher than before (P < 0.05). The blood glucose indexes at the same time point in the optimized group were found to be lower than those in the general group by statistical analysis, but electrolytes were not statistically significant when compared with the general group (P > 0.05). In the optimized group, the time to achieve blood glucose standard (6.59 ± 1.94) d and insulin pumping time (7.14 ± 1.89) d were shorter than those in the general group [(7.48 ± 2.12) d and (8.58 ± 2.14) d], insulin dosage (748.85 ± 63.61) U was less than that in the general group (923.54 ± 84.14) U, and the incidence of hypoglycemia (3.70%) was lower than that in the general group (16.67%), and the satisfaction rate (92.59%) was higher than that of the general group (77.78%), which was statistically significant (P < 0.05). Before intervention, there was no significant difference in NIHSS score and BI score between the two groups (P > 0.05). After 7 d and 14 d of intervention, the NIHSS scores of the two groups were lower than before, while the BI scores were higher than before, and the NIHSS scores of the optimized group at the same time point were all lower than those of the general group, and the BI scores were higher than those of the general group (P < 0.05). The incidence of pulmonary infection (11.11%) and rebleeding (7.41%) in the optimized group were lower than those in the general group (25.93% and 22.22%), while deep vein thrombosis, multiple organ dysfunction syndrome (MODS), and death within 28 d was not statistically significant when compared with the general group (P > 0.05). Conclusion: Optimal management of hyperglycemia and intensive nursing can effectively control the blood sugar level of patients after cerebral hemorrhage, reducing insulin dosage, and the occurrence of hypoglycemia, pulmonary infection, and rebleeding.


Assuntos
Hiperglicemia , Hipoglicemia , Acidente Vascular Cerebral , Glicemia , Hemorragia Cerebral , Controle Glicêmico , Humanos , Hiperglicemia/complicações , Hipoglicemia/complicações , Insulina/uso terapêutico
8.
Comput Math Methods Med ; 2022: 6185739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060652

RESUMO

Objective: To systematically evaluate the effect of nursing intervention on children with type 2 diabetes. Methods: The randomized controlled trials (RCTs) on nursing intervention in children with type 2 diabetes in CNKI, VIP, WanFang, Chinese Biomedical Database (CBM), PubMed, The Cochrane Library, Embase, and Science were searched by the computer until July 2022. Two evaluators reviewed the articles, selected the information, and assessed their quality according to the inclusion criteria and exclusion criteria and then carried out meta-analysis with RevMan 5.3. Results: A total of 5 RCT studies were kept, including 319 patients with type 2 diabetes (≤21 years old), where 162 patients were in the nursing group and 157 patients were in the control group. Meta-analysis revealed that, compared with routine nursing, nursing intervention could effectively control children's fasting blood glucose (FBG) (MD = -1.68, 95% CI (-2.19, -1.17), P < 0.00001), 2 h postprandial blood glucose (2hPG) (MD = -4.01, 95% CI (-4.70, -3.33), P < 0.00001), fasting insulin (FINS) (MD = -7.42, 95% CI (-10.63, -4.20), P < 0.00001), 2 h postprandial insulin (2hINS) (MD = -58.18, 95% CI (-103.24, -13.11), P = 0.01), triglycerides (TG) (MD = -0.41, 95% CI (-0.56, -0.25), P < 0.00001), and systolic blood pressure (SBP) (MD = -8.85, 95% CI (-14.67, -3.03), P = 0.003) and effectively maintain patients' blood glucose at a normal level (MD = -8.85, 95% CI (-14.67, -3.03), P = 0.003), where all the differences were statistically significant. Conclusion: The existing evidence showed that nursing intervention has a significant effect in controlling normal blood glucose and improving insulin utilization in children with type 2 diabetes, which can effectively improve the therapeutic effect on children.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Glicemia , Pressão Sanguínea , Criança , Humanos , Insulina , Adulto Jovem
9.
Comput Math Methods Med ; 2022: 8332278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060656

RESUMO

Patients with type 2 diabetes have twice as much of the risk of acute ischemic stroke (AIS) occurrence as healthy individuals, and the AIS patients with type 2 diabetes have a higher risk of death and a poorer prognosis. This study was to investigate the interrelationship between hyperglycemia and AIS and provided a reference for blood glucose management of AIS patients. The blood glucose level of AIS patients of the present study was controlled by insulin below 180 mg/dL (standard group) and between 80 and 130 mg/dL (management group). And the fasting venous blood samples were collected for determination of blood glucose level, homeostasis model assessment of insulin resistance (HOMA-IR), peptide C, and basal insulin level. Furthermore, lipids of the blood samples were detected using metabolomics, so as to clarify the similarities and differences in metabolic patterns in AIS patients with diabetes after the intervention of different glycemic strategies. The results revealed that compared to the standard group, the blood glucose level and HOMA-IR in the management group were significantly decreased, and levels of peptide C and basal insulin level were greatly increased. Through lipidomics detection, 83, 50, and 44 types of significantly upregulated differential lipids were detected in the standard vs. normal groups, the standard vs. management groups, and the management vs. normal groups, respectively, with triacylglycerol dominated. This study preliminarily revealed metabolic differences among AIS patients with hyperglycemia after different blood glucose intervention methods, hoping to provide a theoretical basis for clinical prevention and treatment of this disease.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , AVC Isquêmico , Glicemia/análise , Cromatografia Líquida , Diabetes Mellitus Tipo 2/complicações , Humanos , Insulina , Lipidômica , Lipídeos , Espectrometria de Massas
10.
Adv Food Nutr Res ; 102: 181-231, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064293

RESUMO

Food proteins, depending on their origin, possess unique characteristics that regulate blood glucose via multiple physiological mechanisms, including the insulinotropic effects of amino acids, the activation of incretins, and slowing gastric emptying rate. The strategies aimed at curbing high blood glucose are important in preventing impaired blood glucose control, including insulin resistance, prediabetes and diabetes. The effect of proteins on blood glucose control can be achieved with high-protein foods short-term, and high-protein diets long-term using foods that are naturally high in protein, such as dairy, meat, soy and pulses, or by formulating high-protein functional food products using protein concentrates and isolates, or blended mixtures of proteins from different sources. Commercial sources of protein powders are represented by proteins and hydrolysates of caseins, whey proteins and their fractions, egg whites, soy, yellow pea and hemp which will be reviewed in this chapter. The effective doses of food protein that are capable of reducing postprandial glycemia start from 7 to 10g and higher per serving; however, the origin of protein, and macronutrient composition of a meal will determine the magnitude and duration of their effect on glycemia. The theoretical and methodological framework to evaluate the effect of foods, including food proteins, on postprandial glycemia for substantiation of health claims on food has been proposed in Canada and is discussed in the context of global efforts to harmonize the international food regulation and labeling.


Assuntos
Glicemia , Controle Glicêmico , Glicemia/metabolismo , Esvaziamento Gástrico , Insulina/farmacologia , Período Pós-Prandial
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 699-708, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36065705

RESUMO

Insulin resistance (IR) is a pathological reaction of hyperinsulinemia and impaired glucose tolerance caused by decreased sensitivity of target tissues such as liver to insulin.The pathogenesis of IR as a typical pathological feature of type 2 diabetes is the focus of anti-diabetes research.In this paper,we reviewed the molecular mechanisms of glucose and lipid metabolism,oxidative stress,mitochondrial dysfunction,endoplasmic reticulum stress,inflammation,and hepatic IR in the case of type 2 diabetes mellitus,which might provide new ideas and theoretical guidance for the treatment of diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Insulina , Fígado , Estresse Oxidativo
12.
JAMA Netw Open ; 5(9): e2230043, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36066894

RESUMO

Importance: Intravenous (IV) insulin infusion is the standard of care for treating diabetic ketoacidosis (DKA) worldwide. Subcutaneous (SC) insulin aspart could decrease the use of health care resources. Objective: To compare the cost-effectiveness of mild uncomplicated DKA management with SC insulin aspart vs IV insulin infusion among pediatric patients from the perspective of a public health care payer using clinical data. Design, Setting, and Participants: This economic evaluation included children aged 2 to 14 years presenting to the emergency department of a single academic medical center with mild DKA between January 1, 2015, and March 15, 2020. The medical records for DKA treatment course and its associated hospitalization costs were reviewed. Data were analyzed from January 1, 2015, to March 15, 2020. Exposures: Subcutaneous insulin aspart vs IV regular insulin infusion. Main Outcomes and Measures: The incremental cost-effectiveness ratio (US dollars per hour), duration of DKA treatment, and length of hospital stay. Results: A total of 129 children with mild DKA episodes (mean [SD] age, 9.9 [3.1] years; 72 girls [55.8%]) were enrolled in the study. Seventy children received SC insulin aspart and 59 received IV regular insulin. Overall, the length of hospital stay in the SC insulin group was reduced (mean, 16.9 [95% CI, -31.0 to -2.9] hours) compared with the IV insulin group (P = .005). The mean (SD) cost of hospitalization in the SC insulin group (US $1071.99 [US $523.89]) was less than that in the IV insulin group (US $1648.90 [US $788.03]; P = .001). The incremental cost-effectiveness ratio was -34.08 (95% CI, -25.97 to -129.82) USD/h. The use of SC insulin aspart was associated with a lower likelihood of prolonged hospital stay (ß = -17.22 [95% CI, -32.41 to -2.04]; P = .03) than IV regular insulin when controlling for age and sex. Conclusion and Relevance: Findings of this economic evaluation suggest that SC insulin aspart is dominant vs IV regular insulin in the management of mild uncomplicated DKA in children.


Assuntos
Diabetes Mellitus , Cetoacidose Diabética , Criança , Análise Custo-Benefício , Diabetes Mellitus/tratamento farmacológico , Cetoacidose Diabética/tratamento farmacológico , Feminino , Humanos , Injeções Subcutâneas , Insulina/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Regular Humana/uso terapêutico
13.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4403-4410, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046869

RESUMO

The present study investigated the anti-oxidative and anti-apoptotic effects and molecular mechanisms of catalpol on the H_2O_2-induced pancreatic ß-cells(INS-1 cells).The oxidative damage model of INS-1 cells was induced and optimized by the stimulation of H_2O_2 of different concentrations for different time.CCK-8 assay was used to detect cell viability after catalpol intervention(1, 5, 10, 20, 40, 80, and 160 µmol·L~(-1)) for 24 h.Intracellular reactive oxygen species(ROS), superoxide dismutase(SOD), and lipid peroxide malondialdehyde(MDA) were measured by DCFH-DA fluorescent probe, WST-1, and TBA respectively.Moreover, the apo-ptotic effect was detected by AO-EB and Annexin V-FITC/PI staining.In addition, the protein expression levels were detected by Wes-tern blot, and intracellular insulin concentration was measured by ELISA.The results showed that the oxidative damage model of INS-1 cells was stably induced by 50 µmol·L~(-1) H_2O_2 treatment for 2 h, and catalpol at 1-80 µmol·L~(-1) did not affect cell viability of INS-1 cells.Compared with the conditions in the model group, 1, 5, and 10 µmol·L~(-1) catalpol intervention for 2 h could protect INS-1 cells from oxidative damage(P<0.001), reduce ROS and MDA, increase SOD, and inhibit excessive cell apoptosis.Moreover, 1, 5, and 10 µmol·L~(-1) catalpol could also up-regulate the phosphorylation of nuclear transcription factor NF-E2 related factors, negatively regulate Kelch-like ECH-associated protein 1(Keap1), phosphorylation of extracellular signal-regulated kinase(ERK), and heme oxyge-nase 1(HO-1), and promote the protein expression of pancreatic-duodenal homeobox factor-1(PDX-1) and glucose transporter 2(GLUT2).In addition, 1, 5, and 10 µmol·L~(-1) catalpol increased insulin secretion of INS-1 cells under oxidative damage in the high-glucose culture medium, indicating function recovery of pancreatic ß cells.PDX-1 is a key nuclear transcription factor of pancreatic ß cell function that directly regulates GLUT2 and insulin synthesis, and affects glucose homeostasis.In conclusion, catalpol can reduce the oxidative damage and apoptosis of INS-1 cells, activate antioxidant pathway, protect the function of pancreatic ß cells, and improve insulin synthesis and secretion.


Assuntos
Células Secretoras de Insulina , Apoptose , Glucose/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Glucosídeos Iridoides , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
14.
PLoS One ; 17(9): e0273675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048792

RESUMO

Psychological problems commonly experienced by patients with type 2 diabetes mellitus (T2DM) cause diabetes fatigue conditions that can further worsen the treatment prognosis. We conducted this investigation to determine the effectiveness of a resilience-based Islamic program on diabetes fatigue and health-related quality of life (HRQoL) by measuring the biochemical indicators of T2DM. This was a quasi-experimental study performed from May to August 2021, in which 80 respondents aged 18-64 years diagnosed with T2DM were included through purposive sampling at a male:female sex ratio of 1:1 in the control group and 17:23 in the treatment group. A resilience-based Islamic program (a combination of stress management, mindfulness, prayer, and dhikr (the ritual formula of Sufi brotherhood recited devotionally in praise of Allah and as a means of attaining ecstatic experience)) was implemented in the treatment group for six sessions by blended online and offline interventions. Multidimensional Fatigue Inventory-20 and World Health Organization Quality of Life, Brief Form were used to evaluate diabetes fatigue and HRQoL. Blood tests were performed to measure HbA1c, total antioxidant serum, insulin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels from baseline to 3 months. Statistical analyses were conducted using paired t test, Wilcoxon signed-rank test, independent t test, and Mann-Whitney U test. The resilience-based Islamic program had a beneficial impact on the levels of HbA1c (p < 0.001), lipid profile (triglyceride) (p = 0.011), HDL-c (p = 0.01), LDL-c (p < 0.001), total antioxidant serum (p = 0.001), insulin (p < 0.001), diabetes fatigue (p < 0.05), and HRQoL (p < 0.05) in patients of the treatment group. The results of biochemical tests related to T2DM also indicated a reduction in diabetes fatigue and an increase in HRQoL due to the resilience-based Islamic program. Considering that a patient's resilience to diabetes is an important factor in the management of diabetes fatigue, the resilience-based Islamic program can be applied at public health centers and community levels to increase T2DM resilience.


Assuntos
Diabetes Mellitus Tipo 2 , Qualidade de Vida , Antioxidantes , Colesterol , HDL-Colesterol , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Fadiga/terapia , Feminino , Hemoglobina A Glicada , Humanos , Insulina , Masculino , Triglicerídeos
15.
Rom J Morphol Embryol ; 63(1): 83-97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074671

RESUMO

BACKGROUND: Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before. AIM: To investigate the effects of alloxan-induced diabetes on rats' lumbar vertebrae, and to assess the potential beneficial impact of arachidonic acid. MATERIALS AND METHODS: Pregnant rats were randomly equally divided into four groups: control, alloxan-induced diabetes received alloxan injection 150 mg∕kg, alloxan + arachidonic acid group received arachidonic acid 10 µg∕animal then given alloxan injection, and arachidonic acid group received it, until offspring age of three weeks. Six male offspring from each group were included in this study at ages of newborn, three-week-old, two-month-old, and their body measurements were recorded. Lumbar vertebrae and pancreas specimens were examined by light microscopy, morphometry, transmission electron microscopy (TEM), and immunohistochemistry for insulin expression. RESULTS: In alloxan-induced diabetes newborn, three-week-old, and two-month-old rats, body measurements were significantly declined, histomorphometry of 6th lumbar vertebrae revealed disorganized chondrocytes, with vacuolated cytoplasm, empty lacunae, diminished matrix staining, with areas devoid of cells. TEM showed shrunken reserve and proliferative cells, with irregular nuclei, and damaged mitochondria. In contrast, alloxan + arachidonic acid group had cytoarchitecture of lumbar vertebrae that were like control group. Histomorphometry of pancreas in alloxan-induced diabetes group showed significant reduction in pancreatic islets number and surface area, damaged pancreatic islet cells appeared atrophied with apoptotic nuclei, and very weak insulin immunostaining. Whereas alloxan + arachidonic acid group displayed healthy features of pancreatic islets, which resembled control group, with strong insulin immunostaining. CONCLUSIONS: Arachidonic acid mitigated alloxan-induced diabetes by its antidiabetic activity.


Assuntos
Diabetes Mellitus Experimental , Ilhotas Pancreáticas , Aloxano/efeitos adversos , Aloxano/metabolismo , Animais , Ácido Araquidônico/efeitos adversos , Ácido Araquidônico/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Feminino , Insulina , Ilhotas Pancreáticas/metabolismo , Vértebras Lombares/metabolismo , Masculino , Gravidez , Ratos
16.
Biomed Pharmacother ; 153: 113405, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076528

RESUMO

Type 2 diabetes mellitus (T2D) is a metabolic disorder that knows no boundaries and is spread across the globe. It is one of the most widely spread metabolic disorder, which has now been described as a 'lifestyle' disease. According to the recent study conducted by International Diabetes Federation, the number of diabetic patients will rise from 463 million to 700 million by the year 2045. Conventional therapies often fail to define clear parameters and did not provide early detection in case of diabetes and pre-diabetes. Due to the limitations associated with these therapies, inclination of research is now focused on developing methods or exploring pathways which can overcome these hurdles. Considering these factors, protein tyrosine phosphatase is considered as a promising molecular level legitimate therapeutic target and is known to negatively regulate leptin and insulin signaling pathways. It has shown to be effective in the management of diabetes mellitus in various in vitro and in vivo studies. Various PTP-1B inhibitors have been studied which had shown promising results in the management of diabetes mellitus and associated complications as well. These inhibitors act by increasing insulin sensitivity by inhibiting PTP-1B mediated insulin pathway. In this article we will review the underlying mechanism of protein tyrosine phosphatase and its inhibitors by various PTP 1-B inhibitors for the management of diabetes mellitus and will further throw some light on the challenges and development of these inhibitors.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Resistência à Insulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Hiperinsulinismo/tratamento farmacológico , Insulina/metabolismo , Resistência à Insulina/fisiologia , Transdução de Sinais
17.
Biomed Pharmacother ; 153: 113450, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076565

RESUMO

This study aimed to prepare and characterize chitosan-Transfersulin (CTI) as an effective intranasal drug delivery system (IDDS) for the treatment of memory disorders by mediating insulin (INS) transport into the brain. Tween 80 was used as an edge activator and chitosan (CS) to increase the elasticity of CTI. CTI nanovesicles were prepared by the film hydration method and characterized after optimization. Optimal values of particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading were found to be 137.9 ± 28.2 nm, 0.20, + 23.4 mV, 65.1 ± 0.9 %, and 9.1 ± 0.4 %, respectively. The TEM image supported these findings. FTIR and TGA also demonstrated suitable entrapment of INS in CTI without any chemical interaction. The circular dichroism and fluorescence spectroscopy results confirmed INS's stability and structural integrity released from the CTI. The nasal uptake of INS loaded into CTI was confirmed by optical fluorescence imaging. Histological inspections of the hippocampus also confirmed the results of the behavioral tests. In conclusion, these nanoformulations exhibited greater neuroprotective effects on rats via increased intracellular drug uptake and sustained retention, and it appears to be a promising and effective IDDS for treating Alzheimer's disease (AD).


Assuntos
Doença de Alzheimer , Quitosana , Nanopartículas , Doença de Alzheimer/tratamento farmacológico , Animais , Quitosana/química , Portadores de Fármacos/química , Insulina/uso terapêutico , Nanopartículas/química , Tamanho da Partícula , Ratos
18.
Rev Med Liege ; 77(9): 538-543, 2022 Sep.
Artigo em Francês | MEDLINE | ID: mdl-36082602

RESUMO

Patients with insulin-treated type 1 diabetes (T1D) are exposed to hypoglycaemia, which may be serious. Serious cognitive impairment (including coma and seizure) that requires the help of a third party is a medical emergency. Besides the intravenous injection of glucose by a health care provider, its treatment consists of the subcutaneous or intramuscular injection of glucagon which may be performed by a family member. However, such an injection is not easy and puts off some people, which retards the initiation of a potentially life-saving therapy. The intranasal administration of 3 mg glucagon has been shown as efficacious as the subcutaneous or intramuscular injection of 1 mg glucagon in controlled studies carried out in both adult and youth patients with T1D. Stimulation and real-life studies among caregivers, patients and acquaintances showed a preference for nasal glucagon because of its easy and quick use. The launch of nasal glucagon (Baqsimi®) offers new perspectives for the ambulatory emergency management of severe hypoglycaemia and hypoglycaemic coma with a special obvious advantage in children.


La personne avec un diabète de type 1 (DT1) traité par insuline est exposée à un risque d'hypoglycémie, parfois grave. L'hypoglycémie sévère qui désigne tout trouble cognitif grave (y compris coma, convulsion) nécessitant l'intervention d'un tiers est une urgence médicale. Outre l'injection de glucose par voie intraveineuse, réservée à un personnel de santé, le traitement consiste en l'injection de glucagon par voie sous-cutanée ou intramusculaire qui peut être réalisée par un membre de l'entourage. Cependant, cette injection n'est pas aisée et rebute certaines personnes, ce qui retarde la mise en route d'un traitement potentiellement salvateur. L'administration nasale de glucagon 3 mg s'est avérée aussi performante que l'injection sous-cutanée ou intramusculaire de 1 mg dans des études contrôlées réalisées chez des patients DT1 adultes ou enfants/adolescents. Des études de simulation et de vraie vie réalisées auprès de soignants, de patients et de connaissances ont montré une préférence pour la forme nasale en raison de sa facilité et rapidité d'utilisation. La commercialisation du glucagon nasal (Baqsimi®) offre de nouvelles perspectives pour le traitement d'urgence ambulatoire de l'hypoglycémie sévère et du coma, avec un avantage particulièrement évident chez les enfants.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Adulto , Glicemia , Criança , Coma/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucagon/efeitos adversos , Glucagon/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina
19.
Cardiovasc Diabetol ; 21(1): 169, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050763

RESUMO

Tirzepatide is the first dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE. Tirzepatide is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake. Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA1c (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent. A sizable proportion of patients (23.0 to 62.4%) reached an HbA1c of < 5.7% (which is the upper limit of the normal range indicating normoglycaemia), and 20.7 to 68.4% lost more than 10% of their baseline body weight. Tirzepatide was significantly more effective in reducing HbA1c and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin. Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses. Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events. For none of the cardiovascular events analysed (MACE-4, or its components) was a hazard ratio > 1.0 vs. pooled comparators found in a meta-analysis covering the whole clinical trial program, and the upper bounds of the confidence intervals for MACE were < 1.3, fulfilling conventional definitions of cardiovascular safety. Tirzepatide was found to improve insulin sensitivity and insulin secretory responses to a greater extent than semaglutide, and this was associated with lower prandial insulin and glucagon concentrations. Both drugs caused similar reductions in appetite, although tirzepatide caused greater weight loss. While the clinical effects of tirzepatide have been very encouraging, important questions remain as to the mechanism of action. While GIP reduces food intake and body weight in rodents, these effects have not been demonstrated in humans. Moreover, it remains to be shown that GIPR agonism can improve insulin secretion in type 2 diabetic patients who have been noted in previous studies to be unresponsive to GIP. Certainly, the apparent advantage of tirzepatide, a dual incretin agonist, over GLP-1RA will spark renewed interest in the therapeutic potential of GIP in type 2 diabetes, obesity and related co-morbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Peso Corporal , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Controle Glicêmico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Metanálise como Assunto , Redução de Peso
20.
Front Endocrinol (Lausanne) ; 13: 983152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120467

RESUMO

Before the advent of TIRF microscopy the fate of the insulin granule prior to secretion was deduced from biochemical investigations, electron microscopy and electrophysiological measurements. Since Calcium-triggered granule fusion is indisputably necessary to release insulin into the extracellular space, much effort was directed to the measure this event at the single granule level. This has also been the major application of the TIRF microscopy of the pancreatic beta cell when it became available about 20 years ago. To better understand the metabolic modulation of secretion, we were interested to characterize the entirety of the insulin granules which are localized in the vicinity of the plasma membrane to identify the characteristics which predispose to fusion. In this review we concentrate on how the description of granule mobility in the submembrane space has evolved as a result of progress in methodology. The granules are in a state of constant turnover with widely different periods of residence in this space. While granule fusion is associated +with prolonged residence and decreased lateral mobility, these characteristics may not only result from binding to the plasma membrane but also from binding to the cortical actin web, which is present in the immediate submembrane space. While granule age as such affects granule mobility and fusion probability, the preceding functional states of the beta cell leave their mark on these parameters, too. In summary, the submembrane granules form a highly dynamic heterogeneous population and contribute to the metabolic memory of the beta cells.


Assuntos
Exocitose , Insulina , Actinas/metabolismo , Cálcio/metabolismo , Exocitose/fisiologia , Insulina/metabolismo , Secreção de Insulina
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