Glucose Balance Research Articles

Empagliflozin Attenuates High-Glucose-Induced Astrocyte Activation and Inflammation via NF-κB Pathway

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (3 d, 3 weeks, and 16 weeks) and treated with EMPA for 3 weeks (NFD, NFD + EMPA, HFD, HFD + EMPA; n = 5/group). EMPA regulated the expression of astrocyte markers and pro-inflammatory cytokine mRNA in the hypothalamus of HFD-induced mice, which was linked to regulation of the NF-κB pathway. Under hyperglycemic conditions, EMPA may mitigate hypothalamic inflammation by modulating astrocyte activation via the NF-κB pathway. Our findings demonstrated that EMPA possesses therapeutic potential beyond merely lowering blood glucose levels, opening new avenues for addressing inflammation and providing neuroprotection in metabolic disease management.

The Association between Social Capital, Food Security, and Type 2 Diabetes Management

Abstract Background Given nutrition’s key role in treating diabetes, food insecurity may seriously affect the standard management of the disease. A patient’s social environment or community plays an important role in managing the disease. This study explores how food security and social capital are associated with the management of type 2 diabetes. Methods A cross-sectional telephone survey of 381 Israelis Jewish and Arab with type 2 diabetes was conducted. Data was collected on food security, social capital, disease management factors, and socioeconomic status. Moreover, medical records provided information about HbA1c, age, and disease diagnosis date for each respondent. Results Blood glucose balance (HbA1c ≤7mmol/mol) was associated with employment, while unemployed respondents had a better balance. Food security is correlated with health perception - the better the food security, the better the health perception. Food security is related to social and family support, as well as to neighborhood help and connections. The social capital index increases as food security increases. A higher disease management index score, as well as a higher trust index score, indicates a more balanced patient. In light of the fact that food security is associated with social aspects of health, it may act as a mediator between social capital and perceived health. Conclusions Social factors directly affect the balance of the disease. Subjective health and gender were associated with food security. Social capital and support are linked to subjective health reporting through food security, so this variable is a mediator. It can be concluded that social factors and food security play a role in subjective health assessment in diabetics. Diabetes management and balancing depend not only on behavioral factors but also on environmental and social factors. Key messages • Food security is a necessary factor in balancing blood glucose levels, as well as a mediator factor between social capital and perceived health among diabetics. • A balanced diabetes requires social support, such as a supportive social environment and must consider the individual’s character.

Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.

Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic-associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro-inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator-activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched-chain ketoacids (BCKAs) and 3-hydroxyisobutyrate (3-HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues-adipose tissue, skeletal muscle, and liver-and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases.

Plasma C24:0 ceramide impairs adipose tissue remodeling and promotes liver steatosis and glucose imbalance in offspring of rats

Fetal programming by exposure to high-energy diets increases the susceptibility to type 2 diabetes mellitus (T2DM2) in the offspring. Glucose imbalance during fetal programming might be associated to still unknown selective lipid species and their characterization might be beneficial for T2DM diagnosis and treatment. We aim to characterize the effect of the lipid specie, C24:0 ceramide, on glucose imbalance and metabolic impairment in cellular and murine models. A lipidomic analysis identified accumulation of C24:0 ceramide in plasma of offspring rats exposed to high-energy diets during fetal programing, as well as in obese-T2DM subjects. In vitro experiments in 3T3L-1, hMSC and HUH7 cells and in in vivo models of Wistar rats and C57BL/6 mice demonstrated that C24:0 ceramide disrupted glucose balance, and differentiation and lipid accumulation in adipocytes, whereas promoted liver steatosis. Mechanistically, C24:0 ceramide impaired mitochondrial fatty acid oxidation in adipocytes and hepatic cells, tentatively by favoring reactive oxygen species accumulation and calcium overload in the mitochondria; and also, activates endoplasmic reticulum (ER) stress in hepatocytes. We propose that C24:0 ceramide accumulation in the offspring followed a prenatal diet exposure, impair lipid allocation into adipocytes and enhances liver steatosis associated to mitochondrial dysfunction and ER stress, leading to glucose imbalance.

A Randomized Controlled Trial to Determine the Impact of Resistance Training versus Aerobic Training on the Management of FGF-21 and Related Physiological Variables in Obese Men with Type 2 Diabetes Mellitus.

Fibroblast growth factor 21 (FGF-21) has been suggested as a potential therapeutic target for insulin resistance in health-related metabolic disorders such as type 2 diabetes. Despite the metabolic effects of resistance (RT) and aerobic training (AT) on diabetes symptoms, uncertainty exists regarding the superiority of effects manifested through these training approaches on FGF-21 and biochemical and physiological variables associated with metabolic disorders in men diagnosed with type 2 diabetes. This study aimed to investigate the impact of a 12-week RT and AT on FGF-21 levels and symptoms associated with metabolic disorders in male individuals diagnosed with type 2 diabetes. Thirty-six sedentary obese diabetic men (40 to 45 years old) were matched based on the level of FGF-1. They and were randomly divided into two training groups (RT, n = 12 and AT, n = 12) performing three days per week of moderate-intensity RT or AT for 12 weeks and an inactive control group (n = 12). Both training interventions significantly improved FGF-21, glucose metabolism, lipid profile, hormonal changes, strength, and aerobic capacity. Subgroup analysis revealed that RT had greater adaptive responses (p < 0.01) in fasting blood sugar (ES = -0.52), HOMA-IR (ES = -0.87), testosterone (ES = 0.52), cortisol (ES = -0.82), FGF-21 (ES = 0.61), and maximal strength (ES = 1.19) compared to AT. Conversely, AT showed greater changes (p < 0.01) in cholesterol (ES = -0.28), triglyceride (ES = -0.64), HDL (ES = 0.46), LDL (ES = -0.73), and aerobic capacity (ES = 1.18) compared to RT. Overall, both RT and AT interventions yielded significant moderate to large ES in FGF-21 levels and enhanced the management of biochemical variables. RT is an effective method for controlling FGF-21 levels and glucose balance, as well as for inducing hormonal changes. On the other hand, AT is more suitable for improving lipid profiles in overweight men with type 2 diabetes mellitus.

Regulation of Energy and Glucose Homeostasis by the Nucleus of the Solitary Tract and the Area Postrema.

The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes.

Regulation of trehalose metabolism mediated by validamycin on chitin synthesis in Spodoptera frugiperda

AbstractTrehalase (TRE) is a key enzyme for degrading trehalose, which plays a vital role in the growth and development of insects. Although validamycin, a compound belonging to a class of efficient antibiotics and fungicides, can control pests by suppressing TRE activities, it remains unknown whether it acts on both trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), a major pest of maize (Zea mays L., Poaceae). This study investigated the changes in trehalose metabolism after validamycin treatment in S. frugiperda and its effects on the downstream chitin synthesis pathway. Compared with the control, S. frugiperda exhibited varying degrees of mortality after treatment with four concentrations of validamycin, showing a dose‐dependent increase in mortality rate. The mortality rates 24 and 48 h after treatment with 0.07 mg μL−1 validamycin were 35.6% and 42.2%, respectively, indicating the effective lethal concentration. Treatment with 0.07 mg μL−1 validamycin led to developmental delay, abnormal molting, and death in S. frugiperda, but it exerted no lasting effects on the survival rate, pupal weight, and phenotype during its subsequent developmental stages. At 24 h after validamycin treatment, TRE1 and TRE2 activities and glucose content decreased significantly, whereas the trehalose content increased significantly. Treatment with validamycin significantly upregulated TRE1 and TRE2 expression after 24 and 48 h and downregulated the mRNA expression of chitin synthase A and B genes. However, after 72 h, chitin content was not significantly affected. Hence, validamycin can destroy the dynamic transformation balance of trehalose and glucose by inhibiting the activities of the two TREs, and further affect the expression of downstream chitin synthase genes. These findings provide a theoretical basis for using TRE inhibitors to control S. frugiperda.

Changes of glycolysis and gluconeogenesis key enzymes in the muscle of the shrimp Penaeus vannamei in response to hypoxia and reoxygenation

Although the shrimp Penaeus vannamei can tolerate oxygen-limited conditions, the organisms may suffer detrimental effects in several processes, including growth, reproduction, immune responses, and others. During hypoxia, the shrimp makes metabolic adjustments in energy use and glucose homeostasis. Glucose is hydrolyzed during glycolysis and synthesized from non-glycosidic metabolites in gluconeogenesis. Although these pathways share many enzymes, the processes are not exactly the reverse of each other. We studied the first and last irreversible steps of glycolysis and gluconeogenesis catalyzed by hexokinase/glucose-6-phosphatase (HK/G6Pase) and pyruvate kinase/pyruvate carboxylase/phosphoenolpyruvate carboxykinase (PK/PC/PEPCK), respectively, in muscle under hypoxia and hypoxia followed by reoxygenation to gain insights about the coordinated metabolic responses that maintain glucose balance during oxygen stress. For the first group, HK gene expression was induced in hypoxia while G6Pase was reduced in hypoxia and reoxygenation, whereas for enzymes activity, HK was maintained and G6Pase was only detected in reoxygenation. For the second group, gene expression increased in PK in hypoxia, in PC in reoxygenation and in both cases, the enzymatic activities were maintained. Mitochondrial PEPCK expression increased during hypoxia and cytosolic PEPCK decreased, while total PEPCK activity was maintained. Intracellular lactate decreased during hypoxia while glucose levels were maintained. Altogether the results show that in limited oxygen, the expression of glycolytic enzymes-genes are induced, the gluconeogenic counterparts are active, although with more varied responses to oxygen limited conditions, and intracellular glucose levels are maintained.

Biology of the proximal tubule in body homeostasis and kidney disease.

The proximal tubule (PT) is known as the workhorse of the kidney, both for the range and magnitude of the functions that it performs. It is not only responsible for reabsorbing most solutes and proteins filtered by glomeruli, but also for secreting non-filtered substances including drugs and uremic toxins. The PT therefore plays a pivotal role in kidney physiology and body homeostasis. Moreover, it is the major site of damage in acute kidney injury and nephrotoxicity. In this review, we will provide an introduction to the cell biology of the PT and explore how it is adapted to the execution of a myriad of different functions and how these can differ between males and females. We will then discuss how the PT regulates phosphate, glucose and acid-base balance, and the consequences of alterations in PT function for bone and cardiovascular health. Finally, we explore why the PT is vulnerable to ischemic and toxic insults, and how acute injury in the PT can lead to maladaptive repair, chronic damage, and kidney fibrosis. In summary, we will demonstrate that knowledge of the basic cell biology of the PT is critical for understanding kidney disease phenotypes and their associated systemic complications, and for developing new therapeutic strategies to prevent these.

Systemic Regulatory Abnormalities in Glycemic Control and its Relation with Depression - A Cross-Sectional Study

Globally, depression is the 3rd leading cause of disability-adjusted life years. The presence of depression and its symptoms has been associated with improper control of glucose and poor glycemic index and a bidirectional relationship was seen between depressive disorders and diabetes mellitus. Depression, even at subclinical levels, has the tendency to increase the risk of incident type 2 diabetes by 25–60%. This study aims to find the prevalence of Type 2 diabetes mellitus(T2DM) in depression patients and to find the relationship between the severity of depression and the severity of T2DM in a Cross-sectional study. A total of 178 patients who attended psychiatry OPD of a tertiary healthcare hospital for a study period of 6 months were recruited into the study after considering inclusion and exclusion criteria evaluated by an experienced psychiatrist. Details like sociodemographic profiles and clinical data related to Major depression and T2DM were collected through self-structured proforma. To assess the severity of depression, HAM-D scale was used and the glycemic severity measure was used to assess the severity of T2DM by a well-trained psychiatrist. Statistical analysis was done and results were framed. The prevalence of Type 2 Diabetes mellitus in depressive disorder patients was found to be 25.2%. A significant association was seen between the severity of T2DM and the severity of depression, with a p-value of 0.013 and a chi-square value of 12.699. Significance with certain clinical factors like insulin usage (F=5.635; p = 0.019) and drug compliance (F=16.841; p &lt;0.001) was seen in T2DM patients with depression. Nearly ¼th of the patients with depression had T2DM and the severity of hyperglycaemia was also found to be high as those patients were on insulin administration, other medical comorbidity disorders were present and drug compliance was found to be poor. Triglyceride glucose index was also found to be high in patients with severe depression, which contributes to improper blood glucose balance. Treating and reducing both the severity of T2DM and depression simultaneously is needed to improve the functioning of the patients and improve the retention in treatment and drug compliance, thereby preventing morbidity and mortality.

Absence of the Peptide Transporter 1 Induces a Prediabetic and Depressive-Like Phenotype in Mice.

Protein-enriched diets improve glycemic control in diabetes or emotional behavior in depressive patients. In mice, these benefits depend on intestinal gluconeogenesis activation by di-/tripeptides. Intestinal di-/tripeptides absorption is carried out by the peptide transporter 1, PEPT1. The lack of PEPT1 might thus alter glucose and emotional balance. To determine the effects of PEPT1 deficiency under standard dietary conditions or during a dietary challenge known to promote both metabolic and cognitive dysfunction, insulin sensitivity, anxiety, and depressive-like traits, hippocampal serotonin (5-HT) and insulin signaling pathway were measured in wild-type (WT) and Pept1-/- mice fed either a chow or a high-fat high-sucrose (HF-HS) diet. Pept1-/- mice exhibited slight defects in insulin sensitivity and emotional behavior, which were aggravated by an HF-HS diet. Pept1-/- mice fed a chow diet had lower hippocampal 5-HT levels and exhibited cerebral insulin resistance under HF-HS diet. These defects were independent of intestinal gluconeogenesis but might be linked to increased plasma amino acids levels. Pept1-/- mice develop prediabetic and depressive-like traits and could thus be used to develop strategies to prevent or cure both diseases.

Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Increased circulating levels of the soluble prorenin receptor (sPRR), a component of the renin angiotensin system (RAS), plays a role in obesity, glucose, and insulin balance. Additionally, studies show that elevated plasma sPRR in diabetic patients is correlated with hyperglycemia in women but not men. Hence, the current study sought to understand the functional role of circulating human sPRR (HsPRR) produced by the adipose tissue (Adi) on adipogenesis and obesity, glucose homeostasis and insulin sensitivity. Adi-HsPRR mice were generated by breeding human sPRR-Myc-tag transgenic mice with mice expressing Adiponectin/Cre. The mouse model was validated by detecting myc-tagged HsPRR in western blot at 28kD. Adi-HsPRR male and female mice were kept on a low-fat (10% kcal from fat; n=4-9/group) or high-fat diet (60% kcal from fat; n=8-13/group) for 20 weeks. Body weight was recorded weekly and body composition (EchoMRI) was assessed monthly. Intraperitoneal glucose tolerance test (ipGTT) was performed at 12 weeks and insulin tolerance test (ITT) at 14 weeks. At 16 weeks, mice were implanted with radio telemeter to measure blood for 5 consecutive days. At the end of the study, tissues and plasma were collected for biochemical analysis and vascular studies. Adipose HsPRR expression did not change circulating sPRR between groups in mice fed a low-fat diet mouse (M: 3.5±0.5 vs 3.9±0.2 ng/ml, F: 2.3±0.2 vs 3.0±0.2 ng/ml) and high fat-fed females (4.3±0.3 vs 5.4±0.5 ng/ml) but increased plasma sPRR in HFD Adi-HsPRR male mice compared to HFD CTL (5.3±0.4 vs 8.7±0.7 ng/ml p&lt;0.05). Yet, Adi-HsPRR expression did not change body weight and composition, glucose, and insulin balance, nor blood pressure and vascular function in male mice regardless the diet. However, Adi-HsPRR improved insulin sensitivity (438±22 vs 360±14 AUC p&lt;0.05) and endothelium-dependent vascular relaxation (11.7±2.6 vs 19.4±2.5 % p&lt;0.05) in Adi-HsPRR female mice fed an HFD. Blood pressure was similar between groups in males and females on both LFD and HFD. Further analysis showed that Adi-HsPRR increased vasodilator agent, Ang 1-7 (5.1±1.6 vs 16.2±3.0 pmol/L p&lt;0.05) in HFD females which was unchanged in HFD males (10.2±2.4 vs 5.2±1.7 pmol/L). Moreover, Adi-HsPRR reduced gene expression of SREBP1C (1.3±0.2 vs 0.7±0.1 2−ΔΔCT p&lt;0.05) and CD36 (1.5±0.3 vs 0.6±0.1 2−ΔΔCT p&lt;0.05), in gonadal white adipose of HFD females but not in males. Additionally, PPAR gamma mRNA was reduced in HFD Adi-HsPRR females (1.1±0.1 vs 0.6±0.1 2−ΔΔCT p&lt;0.05). Our findings suggest that HsPRR in adipose tissue exerts sex-specific protective effects on insulin sensitivity and endothelial function during obesity, despite similar plasma sPRR levels between control and Adi-HsPRR mice. Thus, our model could be a useful tool to investigate potential antidiabetic effect of adipose sPRR in obese women. This work was supported by National Institutes of Health grants (R01-HL-142969 and R01-HL-1647 to ASL); the National Institute of General Medical Sciences (P30 GM127211); and the University of Kentucky, Center for Clinical and Translational Sciences (UL1TR001998). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Time-restricted Eating to Improve Metabolic Health: Investigating the Mechanisms Underlying Glycolytic and Lipolytic actions

Time-restricted eating (TRE) is a behavioral intervention approach motivated by the emerging role of circadian rhythms in physiology and metabolism. In this approach, all caloric intake is restricted within a regular interval of less than 12 hours, with no overt attempt to reduce calories. We present a whole-body computational model of TRE that incorporates enzyme and substrate reactions as well as hormonal actions during fasting and postprandial states. The model is divided into seven compartments: brain, heart, skeletal muscle, gastrointestinal tract, liver, adipose tissue, and other tissues. We conducted simulations to test the hypothesis that TRE modulates whole-body glucose balance by improving postprandial hyperglycemia and hypertriglyceridemia, keeping these excursions to a minimum. We simulated different TRE schedules with meals varying in fat and carbohydrate content. Our results highlight the importance of chrono-pharmacological considerations in glycemic control: TRE modulates the interplay between glycogenolysis in the liver, lipolysis in adipose tissue and fatty acid oxidation in other organs to improve glucose control. The alternation of eating and fasting, in particular, could be manipulated to balance blood sugar levels. TRE simulations have also shown beneficial effects on the lipid front, such as lower triglyceride levels and improved lipolytic effciency, meaning the body is better able to use fat stores for fuel. This work was supported by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hepatic ketone body regulation of renal gluconeogenesis

ObjectivesDuring fasting, liver pivotally regulates blood glucose levels through glycogenolysis and gluconeogenesis. Kidney also produces glucose through gluconeogenesis. Gluconeogenic genes are transactivated by fasting, but their expression patterns are chronologically different between the two organs. We find that renal gluconeogenic gene expressions are positively correlated with the blood β-hydroxybutyrate concentration. Thus, we herein aim to investigate the regulatory mechanism and its physiological implications. MethodsGluconeogenic gene expressions in liver and kidney were examined in hyperketogenic mice such as high-fat diet (HFD)-fed and ketogenic diet-fed mice, and in hypoketogenic PPARα knockout (PPARα−/−) mice. Renal gluconeogenesis was evaluated by rise in glycemia after glutamine loading in vivo. Functional roles of β-hydroxybutyrate in the regulation of renal gluconeogenesis were investigated by metabolome analysis and RNA-seq analysis of proximal tubule cells. ResultsRenal gluconeogenic genes were transactivated concurrently with blood β-hydroxybutyrate uprise under ketogenic states, but the increase was blunted in hypoketogenic PPARα−/− mice. Administration of 1,3-butandiol, a ketone diester, transactivated renal gluconeogenic gene expression in fasted PPARα−/− mice. In addition, HFD-fed mice showed fasting hyperglycemia along with upregulated renal gluconeogenic gene expression, which was blunted in HFD-fed PPARα−/− mice. In vitro experiments and metabolome analysis in renal tubular cells showed that β-hydroxybutyrate directly promotes glucose and NH3 production through transactivating gluconeogenic genes. In addition, RNA-seq analysis revealed that β-hydroxybutyrate-induced transactivation of Pck1 was mediated by C/EBPβ. ConclusionsOur findings demonstrate that β-hydroxybutyrate mediates hepato–renal interaction to maintain homeostatic regulation of blood glucose and systemic acid-base balance through renal gluconeogenesis regulation.

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.

Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction-associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis-inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.

The Role of BDNF and TrkB in the Central Control of Energy and Glucose Balance: An Update.

The global rise in obesity and related health issues, such as type 2 diabetes and cardiovascular disease, is alarming. Gaining a deeper insight into the central neural pathways and mechanisms that regulate energy and glucose homeostasis is crucial for developing effective interventions to combat this debilitating condition. A significant body of evidence from studies in humans and rodents indicates that brain-derived neurotrophic factor (BDNF) signaling plays a key role in regulating feeding, energy expenditure, and glycemic control. BDNF is a highly conserved neurotrophin that signals via the tropomyosin-related kinase B (TrkB) receptor to facilitate neuronal survival, differentiation, and synaptic plasticity and function. Recent studies have shed light on the mechanisms through which BDNF influences energy and glucose balance. This review will cover our current understanding of the brain regions, neural circuits, and cellular and molecular mechanisms underlying the metabolic actions of BDNF and TrkB.

Effects of the kinetic pattern of dietary glucose release on nitrogen utilization, the portal amino acid profile, and nutrient transporter expression in intestinal enterocytes in piglets

BackgroundPromoting the synchronization of glucose and amino acid release in the digestive tract of pigs could effectively improve dietary nitrogen utilization. The rational allocation of dietary starch sources and the exploration of appropriate dietary glucose release kinetics may promote the dynamic balance of dietary glucose and amino acid supplies. However, research on the effects of diets with different glucose release kinetic profiles on amino acid absorption and portal amino acid appearance in piglets is limited. This study aimed to investigate the effects of the kinetic pattern of dietary glucose release on nitrogen utilization, the portal amino acid profile, and nutrient transporter expression in intestinal enterocytes in piglets.MethodsSixty-four barrows (15.00 ± 1.12 kg) were randomly allotted to 4 groups and fed diets formulated with starch from corn, corn/barley, corn/sorghum, or corn/cassava combinations (diets were coded A, B, C, or D respectively). Protein retention, the concentrations of portal amino acid and glucose, and the relative expression of amino acid and glucose transporter mRNAs were investigated. In vitro digestion was used to compare the dietary glucose release profiles.ResultsFour piglet diets with different glucose release kinetics were constructed by adjusting starch sources. The in vivo appearance dynamics of portal glucose were consistent with those of in vitro dietary glucose release kinetics. Total nitrogen excretion was reduced in the piglets in group B, while apparent nitrogen digestibility and nitrogen retention increased (P < 0.05). Regardless of the time (2 h or 4 h after morning feeding), the portal total free amino acids content and contents of some individual amino acids (Thr, Glu, Gly, Ala, and Ile) of the piglets in group B were significantly higher than those in groups A, C, and D (P < 0.05). Cluster analysis showed that different glucose release kinetic patterns resulted in different portal amino acid patterns in piglets, which decreased gradually with the extension of feeding time. The portal His/Phe, Pro/Glu, Leu/Val, Lys/Met, Tyr/Ile and Ala/Gly appeared higher similarity among the diet treatments. In the anterior jejunum, the glucose transporter SGLT1 was significantly positively correlated with the amino acid transporters B0AT1, EAAC1, and CAT1.ConclusionsRational allocation of starch resources could regulate dietary glucose release kinetics. In the present study, group B (corn/barley) diet exhibited a better glucose release kinetic pattern than the other groups, which could affect the portal amino acid contents and patterns by regulating the expression of amino acid transporters in the small intestine, thereby promoting nitrogen deposition in the body, and improving the utilization efficiency of dietary nitrogen.

Medicinal, Nutritional and Health Benefits, Pharmacological Properties of KIWI – A Review

Global health and treatment approaches aim to combine complementary and alternative medicine with evidence-based medicine to better comprehend the human body’s metabolic processes. The kiwi fruit frequently referred to as the "Chinese gooseberry" belongs to the Actinidiaceae family and is classified as Actinidia genus andspecies deliciosa. Kiwi fruit has seen a significant increase in demand recently because of its high vitamin C content.Kiwi fruit is also a great source of antioxidants, carotenoids, iron, and dietary fiber. These could help regulate blood sugar, reduce blood pressure, promote wound healing, and enhance intestinal health. Antioxidants such as vitamin C, choline, lutein, and zeaxanthin help the body eliminate free radicals and may shield the body from a number of illnesses and inflammations. Contributing significantly to the flavonoid and phenolic contents in kiwi fruit, it is a primary source of phytochemicals such as caffeic acid, gallic acid, syringic acid, salicylic acid, ferulic acid, and protocatechuic acid. Numerous pharmacological qualities, such as anti-diabetic, anti- tumor, anti-inflammatory, anti-ulcer, antioxidant activity, hypoglycemia, hypolipidemic, and many more, have been linked to kiwi fruit and its constituents. In addition to these, kiwi fruit is traditionally used to treat microbiological infections, rheumatoid arthritis, hepatitis, edema, and renal issues. The fiber in kiwi fruit promotes the fruit's ability to retain water, which helps to shorten transit times and preserves the person's gastrointestinal health. Studies are also being conducted on the homeostatic balance, weight maintenance, and insulin and glucose balance in relation to kiwi fruit consumption. Keywords: Actinidia deliciosa, Chinese gooseberry, Hypoglycemia, Kiwi, Cancer

Mechanism of Action of Oral Salmonella-Based Vaccine to Prevent and Reverse Type 1 Diabetes in NOD Mice.

A combination therapy of preproinsulin (PPI) and immunomodulators (TGFβ+IL10) orally delivered via genetically modified Salmonella and anti-CD3 promoted glucose balance in in NOD mice with recent onset diabetes. The Salmonella bacteria were modified to express the diabetes-associated antigen PPI controlled by a bacterial promoter in conjunction with over-expressed immunomodulating molecules. The possible mechanisms of action of this vaccine to limit autoimmune diabetes remained undefined. In mice, the vaccine prevented and reversed ongoing diabetes. The vaccine-mediated beneficial effects were associated with increased numbers of antigen-specific CD4+CD25+Foxp3+ Tregs, CD4+CD49b+LAG3+ Tr1-cells, and tolerogenic dendritic-cells (tol-DCs) in the spleens and lymphatic organs of treated mice. Despite this, the immune response to Salmonella infection was not altered. Furthermore, the vaccine effects were associated with a reduction in islet-infiltrating lymphocytes and an increase in the islet beta-cell mass. This was associated with increased serum levels of the tolerogenic cytokines (IL10, IL2, and IL13) and chemokine ligand 2 (CCL2) and decreased levels of inflammatory cytokines (IFNγ, GM-CSF, IL6, IL12, and TNFα) and chemokines (CXCL1, CXCL2, and CXCL5). Overall, the data suggest that the Salmonella-based vaccine modulates the immune response, reduces inflammation, and promotes tolerance specifically to an antigen involved in autoimmune diabetes.

Verifying The Association Between IL6 -174G/C Polymorphism in Type 2 Diabetes Mellitus

Background : Diabetes mellitus, also known as blood sugar, is a series of metabolic disorders described by high blood glucose levels (hyperglycemia), low blood glucose (hypoglycemia), or both, resulting from defects in insulin production, insulin action, or both. Numerous studies have shown that interleukin (IL-6) acts on skeletal muscle cells , liver cells, and pancreas cells to influence glucose balance and metabolism, which directly or indirectly contributes to the development of diabetes. Research in this area is crucial because diabetes is recognized as a major risk factor for many diseases like Diabetic retinopathy, Diabetic nephropathy, Diabetic Neuropathy , heart disease and others. Patients and methods : In this study, we tested three of genotypes GG; GC ; CC for IL6 -174G/C polymorphism to determine its association with type 2 diabetes and its effect on insulin. One hundred T2DM patients and 100 clinically healthy participants were enrolled in the study. Results and Conclusion : Based on the results presented by the researcher, the three genetic polymorphisms GG, GC, and CC of the IL6-174G/C polymorphism did not appear to be associated with type 2 diabetes or determine the course of the disease. Given society’s demand for radical solutions and the necessity of reducing the increasing number of deaths every year, these findings underscore the need for continued research into understanding the complex interplay of factors that contribute to diabetes-related complications.