Insulin Secretion Research Articles

A novel bombesin-related peptide modulates glucose tolerance and insulin secretion in non-obese and hypothalamic-obese rats.

This study investigated the effects of a novel bombesin-related peptide (BR-b), derived from the skin of the Chaco tree frog (Boana raniceps), on glucose homeostasis in non-obese and hypothalamic-obese male rats. Hypothalamic obesity was induced in neonatal rats through high-dose administration of monosodium glutamate (MSG; 4g/kg), while control animals (CTL) received an equimolar saline solution. At 70 days of age, both MSG and CTL groups underwent an oral glucose tolerance test (OGTT; 2g/kg) with or without prior intraperitoneal administration of BR-b at doses of 0.5 or 1.0mg/kg, delivered 5min before the glucose challenge. At 75 days of age, pancreatic islets were isolated and exposed to glucose in the presence or absence of BR-b (1.0 or 5.0μM). MSG-treated rats developed obesity, hyperinsulinemia, and insulin resistance. BR-b administration exacerbated glucose intolerance during the OGTT, particularly at the 1.0mg/kg dose, with more pronounced effects observed in the CTL group. Insulin secretion from pancreatic islets was influenced by both obesity status and glucose concentration. In islets from CTL rats, BR-b (5μM) reduced insulin release under non-stimulatory glucose conditions but enhanced insulin secretion at stimulatory glucose levels. Conversely, in islets from MSG-obese rats, BR-b exhibited an inhibitory effect on insulin release at basal glucose concentrations, while the insulinotropic response to high glucose was abolished. In summary, BR-b administration shortly before the OGTT impaired glucose tolerance and modulated insulin secretion from pancreatic islets in a glucose-dependent manner in non-obese rats. These effects were attenuated or absent in MSG-obese rats, indicating that hypothalamic obesity alters the metabolic responses to bombesin-related peptides.

DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes.

Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored. The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix). DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism. Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.

Differences in VEGF (Vascular Endothelial Growth Factor) Levels AND IGF-1 (Insulin like Growth Factor-1) in Controlled and Uncontrolled Diabetes Mellites TIP 2 Patients at Puskesmas Padang Bulan Medan City

Diabetes mellitus is a metabolic disorder characterized by an increase in blood sugar due to decreased insulin secretion by pancreatic beta cells or impaired insulin function (insulin resistance) that can lead to microvascular and macrovascular complications. The results of previous studies state that plasma levels of VEGF and IGF-1 are associated with the incidence of diabetic retinopathy and diabetic nephropathy. The examinations carried out include HbA1C using the HPLC method, measurement of VEGF and IGF-1 levels using Bioassay Technology Laboratory ELISA Human IGF-1 and VEGF. Of the 52 patients examined, it was found that 10 type 2 DM were controlled and 42 type 2 DM were uncontrolled. Uncontrolled type 2 DM had a higher VEGF level of 409 (ng/ml) than controlled 391.8 (ng/ml). IGF-1 levels of uncontrolled type 2 DM were higher at 8.8 (ng/ml) than controlled 6.6 (ng/ml). The conclusion obtained from this study is that there is no significant difference in VEGF and IGF-1 levels in controlled and uncontrolled type 2 DM. Controlled type 2 DM VEGF levels are lower than uncontrolled, while controlled IGF-1 levels are lower than uncontrolled. There was no significant difference in IGF- 1 levels with obese and non-obese patients based on Body Mass Index (BMI). IGF-1 levels of obese type 2 DM are lower than those who are not obese.

Managing persistent neonatal hyperinsulinemic hypoglycemia: Insights from nesidioblastosis research

Background: Persistent neonatal hyperinsulinemic hypoglycemia (PNHH), frequently associated with nesidioblastosis, poses significant diagnostic and therapeutic challenges due to dysregulated insulin secretion. Congenital hyperinsulinism (CHI), the primary cause of PNHH, exhibits diverse genetic and phenotypic presentations, necessitating tailored management strategies. This review integrates insights from 20 studies, examining genetic, therapeutic, and psychosocial dimensions of CHI. Objectives: To evaluate genotype-phenotype correlations and their implications for therapeutic outcomes in CHI, compare long-term medical and surgical outcomes, and identify risk factors affecting growth, metabolism, and neurodevelopment. Additionally, the study explores effective strategies to address the psychosocial and dietary challenges associated with CHI. Methods: A systematic review of 20 studies, encompassing over 2,000 patients, was conducted. Diagnostic criteria included genetic analyses of mutations in KATP channel genes (ABCC8, KCNJ11), GLUD1, and HNF4A, along with imaging and histopathological assessments. Treatment efficacy, long-term outcomes, and the impact of caregiver burden were analyzed. Data were synthesized into thematic categories, supported by statistical and qualitative assessments. Results: Dominant KATP mutations exhibited high responsiveness to diazoxide (70%), whereas recessive mutations necessitated surgical interventions, particularly near-total pancreatectomy. Focal CHI resolved hypoglycemia effectively with lesionectomy, whereas diffuse CHI presented ongoing risks, including diabetes and neurodevelopmental impairments. Personalized dietary strategies, such as high-protein diets and gastrostomy feeding, were effective in stabilizing glucose levels. Psychological stress in caregivers emerged as a significant concern, emphasizing the need for supportive interventions. Emerging therapies like lanreotide showed promise in refractory CHI cases. Discussion: The findings align with prior research, confirming the role of genetic mutations in determining treatment responsiveness. Surgical interventions, though effective in resolving hypoglycemia, carry long-term metabolic risks. Recent advances in genetic diagnostics and personalized medical therapies highlight opportunities for optimizing outcomes. However, caregiver burden and psychosocial challenges remain underexplored areas that require structured support systems. Conclusion: Managing CHI necessitates a multidisciplinary approach, integrating genetic insights, advanced therapies, and psychosocial support. Continued research is essential to develop innovative solutions for refractory CHI cases and to improve long-term outcomes for patients and families.

NFAT5 exacerbates β-cell ferroptosis by suppressing the transcription of PRDX2 in obese type 2 diabetes mellitus

Pancreatic β-cell damage is a critical pathological mechanism in the progression of obese type 2 diabetes mellitus (T2DM). However, the exact underlying mechanism remains unclear. We established an obese T2DM mouse model via high-fat diet feeding. The protein expression profiles of pancreatic tissues from normal and obese T2DM mice were analyzed, revealing that nuclear factor of activated T cells 5 (NFAT5) and ferroptosis are potential mediators and mechanisms of β-cell damage in obese T2DM mice. In vitro, high glucose and palmitate treatment resulted in increased NFAT5 expression and nuclear translocation in MIN6 cells. Inhibition of NFAT5 expression by shRNA significantly reduced ferroptosis and improved the reduction in insulin secretion in palmitic acid and high glucose (PG)-treated MIN6 cells. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed the ability of NFAT5 to bind to the peroxiredoxin 2 (PRDX2) promoter, leading to the downregulation of PRDX2 transcription. Subsequent rescue experiments confirmed that NFAT5 is involved in PG-induced ferroptosis in MIN6 cells by inhibiting the expression of PRDX2. Finally, we demonstrated that the use of the AAV8-RIP2-miR30-shNFAT5 vector to specifically inhibit the expression of NFAT5 in β-cells significantly diminishes ferroptosis in obese T2DM mice, thereby increasing insulin secretion and improving abnormal glucose tolerance. These findings collectively highlight the therapeutic potential of targeting NFAT5 in β cells to counteract obesity-induced T2DM.

Hallmarks of Quercetin Benefits as a Functional Supplementary in the Management of Diabetes Mellitus-Related Maladies: From Basic to Clinical Applications.

Quercetin (QE), a particular flavonoid, is well known for its medicinal effects, including anti-oxidant, hypoglycemic, and anti-inflammatory effects. In this review, the findings of QE effects on diabetes STZinduced, alloxan-induced, and its complications have been summarized with a particular focus on in vitro, in vivo, and clinical trials. Consequently, QE mediates several mechanisms, including ameliorating tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-8, and IL-10 expression, increasing insulin glucose uptake to inhibit insulin resistance. Moreover, QE stimulates insulin secretion and attenuates insulin resistance through various pathways, namely transient KATP channel, motivating peroxisome proliferator-activated receptor expression, increasing glucose transporter-4, and decreasing inducible nitric oxide synthase in skeletal muscle. QE has protective effects on the complications caused by diabetes, such as polycystic ovary syndrome, high-fat diet-induced obesity, diabetic-induced hepatic damage, vascular inflammation, nephropathy, and neuropathy.

Multi-Omics Sequencing Dissects the Atlas of Seminal Plasma Exosomes from Semen Containing Low or High Rates of Sperm with Cytoplasmic Droplets

Sperm cytoplasmic droplets (CDs) are remnants of cytoplasm that can cause a number of problems if it not shed from the sperm after ejaculation. Exosomes can rapidly bind to sperm, but it is not clear whether exosomes can affect the migration and shedding of CDs. We first extracted and characterized seminal plasma exosomes from boar semen containing sperm with low or high rates of CDs. Then, the transcriptomic and proteomic detection of these exosomes were performed to analyze the differences between the two groups of seminal plasma exosomes. The results revealed that 486 differentially expressed genes (DEGs), 40 differentially expressed proteins (DEPs), and 503 differentially expressed lncRNAs (DElncRNAs) were identified between the low CD rate group and high CD rate group. Integrative multi-omics analysis showed that exosome components may affect migration and shedding of cytoplasmic droplets by influencing cytoskeletal regulation and insulin signaling, including regulation of the actin cytoskeleton, ECM–receptor interaction, axon guidance, insulin secretion, and the insulin signaling pathway. Overall, our study systematically revealed the DEGs, DEPs, and DElncRNAs in seminal plasma exosomes between low CD rate semen and high CD rate semen, which will help broaden our understanding of the complex molecular mechanisms involved in the shedding of CDs.

CORRELATION BETWEEN MAGNESIUM AND CALCIUM LEVELS ON HEALTH IN THE ELDERLY WITH DEGENERATIVE TYPE 2 DIABETES MELLITUS

Diabetes Mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels due to decreased insulin secretion from pancreatic beta cells or insulin resistance. Magnesium and calcium are essential minerals that play crucial roles in various enzymatic activities, significantly influencing important biological functions, particularly in relation to metabolic syndrome. The purpose of the research is to investigate the correlation between magnesium and calcium levels in the serum of elderly individuals with type 2 diabetes mellitus. The study method is descriptive observation with cross-sectional studies. The examination sample used 25 serum samples of people with diabetes with age inclusion criteria over 50 years old without any other degenerative diseases. The analysis of the data from the results of the study was then carried out by the SpSS test of the relationship between magnesium levels and the condition of type 2 DM, especially in the context of aging and its impact on metabolic health. Based on the examination of magnesium levels using the xylidil blue method, 23 patients (92%) showed normal results, while 2 patients (8%) showed numbers above normal on average. There was no significant relationship between blood sugar and magnesium levels, blood sugar with calcium levels, and between magnesium with calcium with a significance of p 0.058, p 0.179, and p 0,114, respectively. The findings of this study could enhance the understanding of the complex interactions between these essential minerals and their potential roles in managing metabolic syndrome, ultimately contributing to better health outcomes for older adults with DM.

Exploring the Role of GLP-1 Receptor Agonists in Alzheimer’s Disease: A Review of Preclinical and Clinical Evidence

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including dulaglutide, liraglutide, semaglutide, and exenatide, are effective treatments for type 2 diabetes mellitus (T2DM) and obesity. These agents mimic the action of the endogenous incretin glucagon-like peptide-1 (GLP-1) by enhancing insulin secretion, inhibiting glucagon release, and promoting weight loss through appetite suppression. GLP-1RAs have recently been suggested to have neuroprotective effects, suggesting their potential as treatment for neurodegenerative disorders, such as Alzheimer’s disease (AD). AD and T2DM share several common pathophysiological mechanisms, including insulin resistance, chronic inflammation, oxidative stress, and mitochondrial dysfunction. These shared mechanisms suggest that therapeutic agents targeting metabolic dysfunction may also be beneficial for neurodegenerative conditions. Preclinical studies on GLP-1RAs in AD models, both in vitro and in vivo, have demonstrated promising neuroprotective effects, including reductions in amyloid-beta accumulation, decreased tau hyperphosphorylation, improved synaptic plasticity, and enhanced neuronal survival. Despite the encouraging results from preclinical models, several challenges need to be addressed before GLP-1RAs can be widely used for AD treatment. Ongoing clinical trials are investigating the potential cognitive benefits of GLP-1RAs in AD patients, aiming to establish their role as a therapeutic option for AD. This review aimed to examine the current literature on preclinical and clinical studies investigating GLP-1 receptor agonists as potential therapeutic agents for AD.

Mechanistic insights on lycopene usage against diabetes and associated complications.

Lycopene is a tetraterpene compound belonging to carotenoids that are widely present in tomatoes and similar products. It is known as a powerful anti-oxidant and a non-provitamin A carotenoid. Lycopene has been found to effectively improve diabetes mellitus and its complications, such as cardiac complications, disorders caused by oxidative stress, and liver and neurological disorders. Furthermore, free radicals have been shown to disrupt the action of insulin by changing the physical state of the target cell membrane, while carotenoids improve insulin secretion and function in blood sugar regulation by neutralizing free radicals. It, therefore, seems that targeted clinical studies are needed to investigate the therapeutic effect of lycopene against metabolic disorders induced by diabetes. This review aims to summarize information on the sources and potential uses of lycopene and the possible mechanisms involved in the reduction of the above diseases. Its protective effects, in terms of toxicity and safety, are also discussed. The literature sources used in this review were PubMed, Google Scholar, Scopus, and Web of Science databases.

The Association Between Glucose Variability and Insulin Parameters in Gestational Diabetes Diagnosed After 24 Gestational Weeks

Background/Objectives: Recently, it was reported that glucose variability (GV) calculated using the 75 g oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes. However, its role in gestational diabetes mellitus (GDM) remains unclear. We investigated the association between GV and insulin parameters in Japanese women diagnosed with GDM after 24 weeks of gestation (late GDM). Methods: A total of 280 mothers with late GDM cared for at Keio University Hospital were included in this study. Using 75 g OGTT, the initial increase and subsequent decrease were calculated as the GV. Results: The initial increase was significantly positively associated with 1 h plasma glucose level (PG) and 2 h PG with 75 g OGTT (p < 0.001), but fasting PG, insulinogenic index (IGI), and homeostasis model assessment—insulin resistance were negatively associated with the initial increase (all p < 0.001). The subsequent decrease was significantly positively correlated with 1 h PG (p < 0.001) but negatively correlated with 2 h PG (p < 0.001), IGI (p = 0.009), and the whole-body insulin sensitivity index derived from the OGTT (p = 0.02). Insulin Secretion-Sensitivity Index-2 was not associated with an initial increase or subsequent decrease. Conclusions: Since the initial increase might reflect insulin secretion and the subsequent decrease might reflect insulin sensitivity in Japanese women with late GDM, GV could alter several insulin parameters. Further studies are required to investigate the usefulness of GV in the management of GDM.

Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers

BackgroundObesity and metabolic syndrome (MetS) have become increasingly significant global health issues. Time-restricted feeding (TRF), as a novel dietary intervention, has garnered attention in recent years. However, there is limited research focusing on the effects of TRF on energy expenditure and systemic low-grade inflammation. This study aims to investigate the impact of TRF on weight management, glucose metabolism, insulin resistance, and lipid metabolism in male C57BL/6J mice, particularly in the context of metabolic disorders induced by a high-fat diet (HFD).MethodsC57BL/6J mice were divided into two groups: a normal diet (ND) group and a high-fat diet (HFD) group. The study duration was 12 weeks. Key parameters observed included body weight, glucose tolerance (via glucose tolerance tests), insulin resistance (HOMA-IR), and insulin secretion under glucose stimulation. Additionally, liver tissue was subjected to Oil Red O staining to assess lipid accumulation, and white and brown adipose tissues were stained with hematoxylin and eosin (HE) to evaluate adipocyte size. The expression of hepatic lipogenesis-related genes (Srebp-c, Chrebp, Fasn, and Acc1) and thermogenic genes in brown adipose tissue (UCP1 and PGC-1α) were also measured. Furthermore, temperature changes in the interscapular brown adipose tissue (BAT) were monitored.ResultsIn the ND group: TRF improved insulin resistance and reduced circulating levels of the pro-inflammatory cytokine IL-6, with a slight reduction in body weight.In the HFD group: TRF significantly mitigated weight gain, improved glucose tolerance and insulin resistance, and enhanced insulin secretion under glucose stimulation. Additionally, TRF reduced hepatic steatosis by downregulating the expression of lipogenesis-related genes in the liver. TRF also increased thermogenesis by upregulating the expression of thermogenic genes (UCP1 and PGC-1α) in BAT, while lowering serum levels of pro-inflammatory cytokines IL-6 and TNF-α, though IL-1β levels remained unchanged.ConclusionThis study demonstrates that TRF can activate thermogenesis in brown adipose tissue and reduce inflammation maker, leading to an improvement in hepatic steatosis and a reduction in white adipose tissue accumulation. These findings suggest that TRF may be a promising intervention for mitigating metabolic disturbances associated with obesity and metabolic syndrome. The study provides mechanistic insights into the beneficial effects of TRF, highlighting its potential in modulating lipid metabolism and exerting anti-inflammatory effects.

Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.

Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of ATP-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets. We also revealed that low-dose quinine (<20 µM) did not directly provoke Ca2+ spikes or insulin secretion under low-glucose conditions but potentiated Ca2+ influx and insulin secretion induced by high glucose, which cannot be explained by KATP inhibition. KCNH6 (hERG2) is a voltage-dependent K+ (Kv) channel that plays a critical role in the repolarization of pancreatic β cells. Patch clamp experiments showed that quinine inhibited hERG channels at low micromolar concentrations. However, whether quinine can target KCNH6 to potentiate glucose-induced insulin secretion remains unclear. Here, we showed that in vivo administration of low-dose quinine (25mg/kg) improved glucose tolerance and increased glucose-induced insulin release in wild-type control mice but not in Kcnh6-β-cell-specific knockout (βKO) mice. Consistently, in vitro treatment of primary islet β cells with low-dose quinine (10 µM) prolonged action potential duration and augmented glucose-induced Ca2+ influx in the wild-type control group but not in the Kcnh6-βKO group. Our results demonstrate that KCNH6 plays an important role in low-dose quinine-potentiated insulin secretion and provide new insights into KCNH6-targeted drug development.

Relationship of asprosin and diabetes: a meta-analysis

BackgroundDiabetes characterized by chronic hyperglycemia, has become a serious hazard to human health in the recent decades. Previous research suggests that asprosin may contribute to the development of diabetes by regulating glucose homeostasis, appetite, insulin secretion, and insulin sensitivity. Although some studies have shown that asprosin levels are higher in patients with diabetes than in healthy individuals, the association between asprosin levels and diabetes remains controversial.AimThis meta-analysis aimed to assess asprosin levels in patients with diabetes and in healthy individuals.MethodsWe searched the following electronic databases: Web of Science, ScienceDirect, PubMed, and Willy. The title or abstract uses the following search term: “diabetes” is used in combination with the term “asprosin.” The meta-analysis results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs).ResultsFourteen articles were included in this meta-analysis. In our meta-analysis, the asprosin level in patients with diabetes was significantly higher than that in healthy controls (SMD: 0.95, 95% CI [0.66, 1.24]). Moreover, there was a significant difference in the asprosin levels between patients with diabetes without complication and those with complication (SMD: 0.81, 95% CI [0.33, 1.29]).ConclusionsThis systematic review is the first to evaluate the relationship between asprosin levels and diabetes. The asprosin levels were significantly higher in patients with diabetes.Clinical trial numberNot applicable.

Insulinotropic and anti-obesity properties of ethno-medicinal plants: pharmacology-based and in-silico predictions

The herbal extracts of four traditional plants; namely Gymnema sylvestre leaves, Garcinia cambogia fruits, Cleome droserifolia leaves, and Nigella sativa seeds, were identified for their main constituents using UHPLC/QTOF-MS/MS. Then, a pharmacology-based analysis and molecular docking verification were established targeting the evaluation of each individual herbal extract for their antidiabetic/anti-obesity potential besides their safety. Streptozotocin-induced diabetic rats were used to evaluate antiobesity and insulinotropic effects against insulin (10 U/Kg, IP) and metformin (100 mg/Kg, per oral) as standard regimens. Levels of insulin and fasting blood glucose as well as body weight were assessed, together with certain histopathological, hematological, and biochemical parameters to establish safety profiles. The four herbal extracts exhibited an increase in insulin secretion in-vivo, which is confirmed by docking studies. The herbal extracts (100 mg/kg per oral, daily) demonstrated a significant weight decrease. Each individual herbal extract markedly improved the streptozotocin-induced indices alterations.

Hypomagnesemia, insulin secretion and action in patients without diabetes, 1 year after kidney transplantation

IntroductionHypomagnesemia after kidney transplantation has been reported as a potential risk factor for development of post-transplant diabetes mellitus.MethodsIn kidney transplant recipients undergoing an oral glucose tolerance test during one-year surveillance follow-up we estimated insulin sensitivity with the Matsuda index, a modified Stumvoll index, and HOMA-2IR. First and second phase insulin secretion was assessed using the Stumvoll equation. Participants were categorized into tertiles by plasma magnesium levels, (&amp;lt;0.7, 07–0.78,&amp;gt;0.78 mmol/L).ResultsWe included 208 patients (62% men, median age 51 years). Patients in the lowest compared to the highest magnesium tertile had higher measured GFR (mean 59 vs. 49 mL/min, p = 0.002), tacrolimus trough concentration (mean 6.7 vs. 5.5 μg/L, p &amp;lt; 0.001), and fasting plasma glucose (mean 5.5 vs. 5.3 mmol/L, p = 0.03). There was no significant difference in the Matsuda index between magnesium tertiles, nor in insulin sensitivity assessed by modified Stumvoll index, HOMA-2IR, first or second phase insulin. Results indicate a non-significant trend toward lower disposition index in the lowest vs. highest tertile (p = 0.052).ConclusionIn kidney transplant recipients with lower compared to normal plasma magnesium levels we found a higher fasting plasma glucose but no differences in insulin sensitivity indexes nor dynamic insulin measurements.

Short- and long-term glycemic effects of pasireotide in patients with acromegaly: a comprehensive case study with review of literature.

Pasireotide (PAS), a multireceptor somatostatin analog, has been demonstrated to effectively control hormone levels, including those of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly. However, it induces hyperglycemia by inhibiting insulin secretion via somatostatin receptor 5 (SSTR5). Despite the extensive literature on the occurrence of PAS-induced hyperglycemia, there is still no consensus on the optimal first-line treatment for this complication. Herein, we present two cases of acromegaly treated with PAS and highlight its short- and long-term effects on glucose metabolism. In the first case, postprandial hyperglycemia manifested rapidly following the commencement of PAS treatment and was effectively managed with dulaglutide under continuous glucose monitoring (CGM). In the second case, long-term PAS therapy resulted in a dose-dependent glycemic response that was controlled by different GLP-1 receptor agonists (GLP-1RAs), including semaglutide. CGM facilitated the early detection of significant glycemic fluctuations, underscoring the necessity for close monitoring in patients receiving PAS therapy. These cases demonstrate the efficacy of GLP-1RAs in managing PAS-induced hyperglycemia and highlights the value of CGM in early detection and intervention. Our findings suggest that GLP-1RAs, particularly semaglutide, are a valuable treatment option for this condition. Further research is needed to determine the optimal treatment strategy, particularly in East Asian populations, and to establish a clear consensus on the first-line therapy for PAS-induced hyperglycemia.

Mechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications.

Loss of pancreatic islet cell mass and function is one of the most important factors in the development of type 2 diabetes mellitus, and hyperglycemia-induced lesions in other organs are also associated with apoptosis or hyperproliferation of the corresponding tissue cells. The Hippo signaling pathway is a key signal in the regulation of cell growth, proliferation and apoptosis, which has been shown to play an important role in the regulation of diabetes mellitus and its complications. Excessive activation of the Hippo signaling pathway under high glucose conditions triggered apoptosis and decreased insulin secretion in pancreatic islet cells, while dysregulation of the Hippo signaling pathway in the cells of other organ tissues led to proliferation or apoptosis and promoted tissue fibrosis, which aggravated the progression of diabetes mellitus and its complications. This article reviews the mechanisms of Hippo signaling, its individual and reciprocal regulation in diabetic pancreatic pathology, and its emerging role in the pathophysiology of diabetic complications. Potential therapeutics for diabetes mellitus that have been shown to target the Hippo signaling pathway are also summarized to provide information for the clinical management of type 2 diabetes mellitus.

Physiological Fatty Acid-Stimulated Insulin Secretion and Redox Signaling Versus Lipotoxicity.

Significance: Type 2 diabetes as a world-wide epidemic is characterized by the insulin resistance concomitant to a gradual impairment of β-cell mass and function (prominently declining insulin secretion) with dysregulated fatty acids (FAs) and lipids, all involved in multiple pathological development. Recent Advances: Recently, redox signaling was recognized to be essential for insulin secretion stimulated with glucose (GSIS), branched-chain keto-acids, and FAs. FA-stimulated insulin secretion (FASIS) is a normal physiological event upon postprandial incoming chylomicrons. This contrasts with the frequent lipotoxicity observed in rodents. Critical Issues: Overfeeding causes FASIS to overlap with GSIS providing repeating hyperinsulinemia, initiates prediabetic states by lipotoxic effects and low-grade inflammation. In contrast the protective effects of lipid droplets in human β-cells counteract excessive lipids. Insulin by FASIS allows FATP1 recruitment into adipocyte plasma membranes when postprandial chylomicrons come late at already low glycemia. Future Directions: Impaired states of pancreatic β-cells and peripheral organs at prediabetes and type 2 diabetes should be revealed, including the inter-organ crosstalk by extracellular vesicles. Details of FA/lipid molecular physiology are yet to be uncovered, such as complex phenomena of FA uptake into cells, postabsorptive inactivity of G-protein-coupled receptor 40, carnitine carrier substrate specificity, the role of carnitine-O-acetyltransferase in β-cells, and lipid droplet interactions with mitochondria. Antioxid. Redox Signal. 00, 000-000.

Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet.

People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion-rather than insulin resistance-is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS+Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.