Insulin Uptake Research Articles

Intestinal-Target and Glucose-Responsive Smart Hydrogel toward Oral Delivery System of Drug with Improved Insulin Utilization.

An intelligent insulin delivery system targeting intestinal absorption and glucose responsiveness can enhance the bioavailability through oral insulin therapy, offering promising diabetes treatment. In this paper, a glucose and pH dual-response polymer hydrogel using carboxymethyl agarose modified with 3-amino-phenylboronic acid and l-valine (CPL) was developed as an insulin delivery carrier, exhibiting excellent biocompatibility and effective insulin encapsulation. The insulin encapsulated in the hydrogel (Ins-CPL) was released in a controlled manner in response to the in vivo stimulation of blood glucose and pH levels with higher levels of intracellular uptake and utilization of insulin in the intestinal environment simultaneously. Notably, the Ins-CPL hydrogel effectively regulated blood sugar in diabetic rats over a long period by simulating endogenous insulin, responding to changes in plasma pH and glucose levels, and overcoming the intestinal epithelium barrier. This indicates a significant boost in oral insulin bioavailability and broadens its application prospects.

Effects of Age and Diet on Triglyceride Metabolism in Mice.

Both age and diet can contribute to alterations in triglyceride metabolism and subsequent metabolic disease. In humans, plasma triglyceride levels increase with age. Diets high in saturated fats can increase triglyceride levels while diets high in omega-3 fatty acids decrease triglyceride levels. Here we asked how age and long-term diet effected triglyceride metabolism in mice. We fed male and female mice a low-fat diet, a western diet, or a diet high in polyunsaturated and omega-3 (n-3) fatty acids for up to 2 years. We measured survival, body composition, plasma triglyceride levels, chylomicron clearance, and oral fat, glucose, and insulin tolerance. Triglyceride levels in mice did not increase with age, regardless of diet. Oral fat tolerance increased with age, while chylomicron clearance remained unchanged. Mice fed western diet had decreased survival. Interestingly, mice fed the n-3 diet gained more lean mass, and had lower insulin levels than mice fed either low-fat or western diet. Moreover, triglyceride uptake into the hearts of mice fed the n-3 diet was strikingly higher than in other groups. In mice, age-induced changes in triglyceride metabolism did not match those in humans. Our data suggested that mice, like humans, had decreased fat absorption with age, but plasma triglyceride clearance did not decrease with age in mice, resulting in lower plasma triglyceride levels and improved oral fat tolerance with age. A chronic diet high in n-3 fatty acids increased insulin sensitivity and uptake of triglycerides specifically into the heart but how these observations are connected is unclear.

Nanomedicine in the Treatment of Diabetes.

Nanomedicine could improve the treatment of diabetes by exploiting various therapeutic mechanisms through the use of suitable nanoformulations. For example, glucose-sensitive nanoparticles can release insulin in response to high glucose levels, mimicking the physiological release of insulin. Oral nanoformulations for insulin uptake via the gut represent a long-sought alternative to subcutaneous injections, which cause pain, discomfort, and possible local infection. Nanoparticles containing oligonucleotides can be used in gene therapy and cell therapy to stimulate insulin production in β-cells or β-like cells and modulate the responses of T1DM-associated immune cells. In contrast, viral vectors do not induce immunogenicity. Finally, in diabetic wound healing, local delivery of nanoformulations containing regenerative molecules can stimulate tissue repair and thus provide a valuable tool to treat this diabetic complication. Here, we describe these different approaches to diabetes treatment with nanoformulations and their potential for clinical application.

Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via Nrf2/HO-1 pathway

Type 2 diabetes causes high blood sugar due to insulin malfunction and is linked to male infertility. Using proniosomes can enhance the effectiveness of Glibenclamide, a medication that stimulates insulin secretion. In our study, male rats with diabetes were treated with GLB with or without proniosomal for 14 days. Proniosomal formulations maintained glucose levels prevented weight loss and showed normal testicular tissue.GLB-proniosomal reduces ROS caused by T2DM through Nrf2, HO-1 pathway and increases CAT, SOD, and GSH production in response to insulin and glucose uptake. The reference and proniosomal treatments showed CAT and SOD significant enzymatic elevation compared to the positive and negative control. CAT significantly correlated with Gpx4 expression with P = 0.0169 and r = 0.98; similarly, the enzymatic activity of SOD also showed a positive correlation between the average glucose levels (r = 0.99 and P = 0.0037). Intestinally, GSH analysis revealed that only proniosomal-GLB samples are significantly elevated from the positive control, with a P value of 0.0210. The data showed proniosomal-GLB was more effective than pure GLB, confirmed by higher Nrf2 (2.050 folds), HO-1 (2.148 folds), and GPx4 (1.9 folds) transcript levels relative to the control with less sample diversity compared to the reference samples, indicating proniosomal stabilized GLB in the blood.Administering GLB and proniosomes formulation has effectively restored testicular function and sperm production in diabetic rats by regulating ROS levels and upregulating anti-ROS in response to glucose uptake. These findings may lead to better treatments for diabetic patients who have infertility issues.

Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; β-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and β-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Triglyceride/HDL cholesterol ratio: the role of the laboratory as an indicator of insulin resistance

Introduction: insulin resistance or insulin resistance (IR) is defined by the reduction in the processes of insulin uptake, to stimulate the use of glucose in different tissues and to eliminate the production and output of hepatic glucose. On the other hand, currently there are different standard methods to evaluate IR, but these types of methods are highly expensive and their processing requires time. Objective: the objective of the literature review was to analyze the triglyceride/HDL cholesterol ratio and the role of the laboratory as an indicator of insulin resistance. Methods: to carry out the bibliographic review article, a documentary exploration method was used through a search for information in databases of journals such as Google Scholar, Pubmed, Scopus, Elsevier, SciELO and Medline. Results: the articles analyzed provide relevant information on the TG/HDL-C ratio and the importance of the laboratory as an indicator to predict and evaluate insulin resistance. Relevant information was also found on dyslipidemias and the different methods used for evaluation of the IR. Conclusion: the triglycerides/HDL-C ratio is of utmost importance in the early diagnosis of insulin resistance, since in the studies reviewed a high value of this ratio is consistent with IR

A Comparative Clinical Study to Determine the Efficacy of Bhudhatrayadi Yoga and Metformin in the Management of Madhumeha w.s.r. to Type II Diabetes Mellitus

Prameha is a chronic disease that is described in all the classics of Ayurveda. Madhumeha is categorised as a subtype of Vataja Prameha. Vata Dosha is mainly vitiated in Madhumeha. The patient passes large quantity of urine which is Kashaya (astringent), Madhura (sweet), Pandu (pale) and Ruksha (dry). Madhumeha is the final stage of all the Prameha when left untreated for long time becomes difficult to treat. In modern medicine signs and symptoms of Madhumeha resembles Type II Diabetes Mellitus. Diabetes is a metabolic disease and is characterised by increase in blood glucose levels, deficiency of insulin or resistance to insulin uptake. 40 patients were selected from the IPD and OPD of Kayachikitsa Department of R.G.G.P.G. Ayurvedic College and Hospital, Paprola, Himachal Pradesh. 20 patients were managed with Bhudhatrayadi Yoga and 20 patients were managed with Tablet Metformin. Bhudhatrayadi Yoga showed moderate improvement in subjective parameters of Madhumeha in the study.

Low Density Lipoprotein Receptor-related Protein 2 Expression and Function in Cultured Astrocytes and Microglia.

Activation of glial cells, astrocytes and microglia, has been observed in neurodegenerative diseases including Alzheimer's disease (AD). Amyloid β (Aβ), which is aggregated and the aggregation is detected as characteristic pathology in AD brain, is known to be produced by neurons and to activate glial cells. Clearance of Aβ from the brain via active transport system is important to prevent the accumulation and aggregation. Low density lipoprotein receptor-related protein 2 (LRP2/megalin) is an Aβ transporter. However, expression and contribution of LRP2 in astrocytes and microglia remain to be clarified. In the present study, we examined the expression of LRP2 and its roles in cultured astrocytes prepared from rat embryonic brain cortex and mouse microglial cell line BV-2. Both cultured rat astrocytes and BV-2 cells expressed LRP2 mRNA detected by RT-PCR. When lipopolysaccharide (LPS) or all-trans retinoic acid (ATRA) were added to BV-2 cells, LRP2 mRNA expression and uptake of microbeads, Aβ and insulin were increased. On the other hand, LPS decreased LRP2 expression and uptake of Aβ and insulin in cultured astrocytes. Knockdown of LRP2 using siRNA attenuated the LPS- or ATRA-increased uptake of microbeads, Aβ and insulin in BV-2 cells. These results suggest that LRP2 was expressed in both astrocytes and microglia and might be involved in endocytosis activities. Adequate control of LRP2 expression and function in astrocytes and microglia might regulate Aβ and insulin levels in brain and would be a potential target in AD pathology.

Intranasal insulin for COVID-19-related smell loss.

Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®. Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3-18months and who persisted with anosmia or hyposmia. The sample size was calculated with "satulator". The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40IU of NPH insulin were placed on the nasal roof of each nostril for 15min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment. 27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63-71) compared to the final mean of 83% (80-86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration. The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

Optimal Management of Insulin in Patients Undergoing 18F-Fluorodeoxyglucose Positron Emission Tomography Scans

ObjectiveThe management of insulin injections and insulin pumps before 18F-fluorodeoxyglucose-positron emission tomography integrated computerized tomography (FDG-PET/CT) scans is an important area to investigate given the rising rate of diabetes, the significant association between diabetes and cancer, and the complex relationship among glucose, insulin, and FDG tumor uptake. The purpose of this study was to determine the recommendations around subcutaneous insulin administration, insulin pumps, and hybrid closed-loop systems before FDG-PET scans. MethodsWe examined the websites of 100 hospitals selected from the 2022 US News and World Report top cancer hospitals for specific strategies around diabetes medication management before FDG-PET/CT scans. ResultsOf the 100 hospital websites, 61 had instructions addressing patients with diabetes. Of the 61 hospitals, 47.5% (n = 29) referred patients to their provider for further instructions, 18% (n = 11) referred patients to their own internal radiology department for further instructions, 16.4% (n = 10) had instructions on oral diabetic medications, 23% (n = 14) had instructions on insulin, and 3.3% (n = 2) had instructions on insulin pump management. Most commonly, instructions were to stop insulin 3 to 4 hours before the study and direct patients to their referring provider for more detailed instructions (n = 7). ConclusionThere is a lack of guidance and consensus among US cancer hospitals on managing insulin and continuous subcutaneous insulin infusions before FDG-PET/CT studies and a majority rely on referring providers to advise patients. However, society guidelines offer inconsistent recommendations and little research has been carried out to help guide referring providers. A multidisciplinary panel of specialists could help to guide practitioners on optimal management.

Identifying the impact of health insurance on subgroups with changing rates of diagnosis.

Expanded access to health care often leads to new diagnoses for previously undetected conditions. New diagnoses make it difficult to identify the causal effect of expanding health insurance on individuals with particular diagnoses: the newly diagnosed in the treatment group are likely to differ in unobserved ways from the control group. This paper provides two methods for dealing with this problem depending on the data available to the researcher and diagnosis-specific knowledge. If there is no panel dimension to the data, then the causal effect for the subgroup of interest can be bounded from either above or below depending on the condition in question. If panel data are available, then the newly diagnosed can be identified, and their treated outcomes subtracted from the overall effect of interest. I apply these methods to find that the difference-in-discontinuities estimator underestimates the effect of Medicare prescription drug coverage on the uptake of insulin by first-time users by 20%.

Stereoisomer-Dependent Membrane Association and Capacity for Insulin Delivery Facilitated by Penetratin.

Cell-penetrating peptides (CPPs), such as penetratin, are often investigated as drug delivery vectors and incorporating d-amino acids, rather than the natural l-forms, to enhance proteolytic stability could improve their delivery efficiency. The present study aimed to compare membrane association, cellular uptake, and delivery capacity for all-l and all-d enantiomers of penetratin (PEN) by using different cell models and cargos. The enantiomers displayed widely different distribution patterns in the examined cell models, and in Caco-2 cells, quenchable membrane binding was evident for d-PEN in addition to vesicular intracellular localization for both enantiomers. The uptake of insulin in Caco-2 cells was equally mediated by the two enantiomers, and while l-PEN did not increase the transepithelial permeation of any of the investigated cargo peptides, d-PEN increased the transepithelial delivery of vancomycin five-fold and approximately four-fold for insulin at an extracellular apical pH of 6.5. Overall, while d-PEN was associated with the plasma membrane to a larger extent and was superior in mediating the transepithelial delivery of hydrophilic peptide cargoes compared to l-PEN across Caco-2 epithelium, no enhanced delivery of the hydrophobic cyclosporin was observed, and intracellular insulin uptake was induced to a similar degree by the two enantiomers.

Theta‐Gamma Phase‐Amplitude Coupling Deficit in Streptozotocin AD Rat Model

AbstractBackgroundTheta rhythms are known to encode sensory information and reflect their effect into gamma oscillations through a modulation process known as theta‐gamma phase‐amplitude coupling (PAC) (Amemiya et al., Cell Reports 2018). The role of the PAC as a network‐level indicator of cognitive impairment in disorders such as dementia and Alzheimer’s disease has received much attention recently (Zheng et al. Nature communication 2020).Injection of Streptozotocin (STZ) in animals is reported to cause resistance to insulin uptake in the brain, leading to memory and cognitive impairment (Kamat, Neural Regeneration Research 2015). The current study examines the induced deficit in the PAC as an early indicator of neurodegenerative effects of STZ.Method3 adult male Wistar rats were included in this study (270 – 300 g). Intraventricular injection of STZ was performed at a dose of 3 mg / Kg with a volume of 10 μl. Two stainless steel electrodes were implanted in the hippocampus (CA1) and medial prefrontal cortex (mPFC). The rats were free to move during recording. LFP data were recorded and segmented into windows of 20 s. Preprocessing and noisy trial rejection were employed for artifact removal, and the theta‐gamma PAC was measured using the mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).ResultOne week after STZ injection, the theta‐gamma PAC values did not show a significant change but after two weeks variation was observed. During this period, the power of different frequency bands was also measured and no significant change was observed even after two weeks. Theta‐gamma PAC deficiency was observed in both regions (CA1 and mPFC).ConclusionSTZ’s intracerebro‐ventricular injection is known to produce cognitive deficits along with an increase in Aβ deposition. This study reports that cross‐frequency coupling deficiency is also observed in this AD mouse model. Moreover, the PAC deficit was detected earlier than any change was observed in the spectral analysis of the data, suggesting that it can serve as a diagnosis tool for memory impairment due to neurodegeneration in the STZ mouse model of AD.

Central nervous system insulin signaling can influence the rate of insulin influx into brain

BackgroundInsulin transport across the blood-brain barrier (BBB) is a highly regulated, saturable process, known to be affected by many peripheral substrates including insulin itself and triglycerides. This is in contrast to insulin leakage into peripheral tissues. Whether the central nervous system (CNS) can control the rate of insulin uptake by brain remains to be determined. Insulin BBB interactions are impaired in Alzheimer’s disease (AD) and CNS insulin resistance is widely prevalent in AD. Therefore, if CNS insulin controls the rate of insulin transport across the BBB, then the defective transport of insulin seen in AD could be one manifestation of the resistance to CNS insulin observed in AD.MethodsWe investigated whether enhancing CNS insulin levels or induction of CNS insulin resistance using an inhibitor of the insulin receptor altered the blood-to-brain transport of radioactively labeled insulin in young, healthy mice.ResultsWe found that insulin injected directly into the brain decreased insulin transport across the BBB for whole brain and the olfactory bulb in male mice, whereas insulin receptor blockade decreased transport in female mice for whole brain and hypothalamus. Intranasal insulin, currently being investigated as a treatment in AD patients, decreased transport across the BBB of the hypothalamus.ConclusionsThese results suggest CNS insulin can control the rate of insulin brain uptake, connecting CNS insulin resistance to the rate of insulin transport across the BBB.

Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.

Patients with type 2 diabetes exhibit severe impairments in insulin signalling in the brain and are five times more likely to develop Alzheimer's disease. However, what leads to these impairments is not fully understood. Here, we show reduced expression of endothelial cell caveolin-1 (Cav-1) in the db/db (Leprdb) mouse model of type 2 diabetes. This reduction correlated with alterations in insulin receptor expression and signalling in brain microvessels as well as brain parenchyma. These findings were recapitulated in the brains of endothelial cell-specific Cav-1 knock-out (Tie2Cre; Cav-1fl/fl) mice. Lack of Cav-1 in endothelial cells led to reduced response to insulin as well as reduced insulin uptake. Furthermore, we observed that Cav-1 was necessary for the stabilization of insulin receptors in lipid rafts. Interactome analysis revealed that insulin receptor interacts with Cav-1 and caveolae-associated proteins, insulin-degrading enzyme and the tight junction protein Zonula Occludence-1 in brain endothelial cells. Restoration of Cav-1 in Cav-1 knock-out brain endothelial cells rescued insulin receptor expression and localization. Overall, these results suggest that Cav-1 regulates insulin signalling and uptake by brain endothelial cells by modulating IR-α and IR-β localization and function in lipid rafts. Furthermore, depletion of endothelial cell-specific Cav-1 and the resulting impairment in insulin transport leads to alteration in insulin signalling in the brain parenchyma of type 2 diabetics.

Pharmacist Participation in Diabetes-Related Distress Assessment and Role of Self Management Among Type-2 Diabetes Mellitus Patients in a Tertiary Care Hospital

According to the World Health Organization (WHO), diabetes is a state of chronic hyperglycemia resulting from decrease in insulin engenderment (type 1) (or) decremented insulin uptake by cells (type 2) leading to multitude of complications ranging from diseases of the diminutive vessels of kidney and retina, peripheral neuropathy and coronary artery disease. Diabetes distress is defined as patient concerns about disease management, support, emotional burden and access to care, is an important condition distinct from depression. It is a part of diabetes and it is a non-psychiatric disease. Diabetes related distress (DRD) refers to the emotional and behavioural changes caused by diabetes. A p-value of less than 0.05 is considered significant. Our study shows the scores of specific diet does not show significant correlation in DDS-17 (r=-0.101) whereas a significant correlation was found in SDSCA (0.206). Similarly, the scores in exercise does not show a significant correlation in DDS-17 (r=0.03) but shows a significant correlation in SDSCA (0.666). It reveals Patients tend to have high and low diabetes distress depending upon their diabetes self-care specifically related to diet intake. Moreover women are more prone to experience diabetes distress. This was confirmed by using the (DDS-17) and (SDSCA). Age, smoking, alcohol, consumption, emotional burden, physical inactivity was found to contribute to the development of diabetes related distress in the study subjects.

Illness Perception and Medication Adherence among Adult Patients with Type 2 Diabetes Mellitus: A Scoping Review

(1) Background: Type 2 diabetes mellitus (T2DM) is a global disease with a compelling impact on developed and developing economies across the globe. The World Health Organization (WHO) (2020) reported a global prevalence of 8.5% in 2014 among adults aged at least 18 years. Consequently, the condition led to a 5% increase in premature mortality from 2000 to 2016. Aim: The scoping review sought to examine illness perception and medication adherence among adult patients with T2DM. (2) Methods: The study was conducted in 2021 and covered articles published in English in the last five years. PubMed, MEDLINE, CINAHL, and ScienceDirect were the primary search engines used to generate the required scholarly records. A total of 20 studies met the inclusion criteria. (3) Results: The 20 studies selected for the scoping review covered different themes on the overall concept of illness perception and medication adherence in adults with Type 2 Diabetes Mellitus. Each study presented unique implications for research and influence on the policymaking relating to the treatment or the management of type 2 diabetes mellitus in adults of different aged groups. (4) Conclusions: The studies reveal both high and low adherence to medications in adults with type 2 diabetes mellitus. The management and treatment of the condition depend on the uptake of oral hypoglycemic agents or insulin as well as the recommended therapies to enhance the clinical outcomes of the patients.

Endocrine System Related to Diabetes Mellitus

Diabetes mellitus has a complicated and poorly understood pathogenesis. However, it turns out to be an abnormal metabolic state linked to systemic vascular bed injury. Additionally, the endocrine system is not functioning normally in people with diabetes mellitus, according to the body of data. Uncertainty surrounds the relationship between the alterations in the endocrine system and the hormonal environment caused by aberrant glucose and fat metabolism, decreased insulin action, or both. A review of the literature shows that the entire endocrine system, including the hormones produced by the hypothalamus, pituitary, adrenal, thyroid, and parathyroid glands as well as the vitamin D system, the gonads, and the adipose tissue, is dysfunctional. Some of these abnormalities may be corrected with proper metabolic management and insulin therapy. It is still unknown how much these endocrine system changes contribute to the vascular pathologies seen in people with diabetes mellitus and whether some of the abnormalities seen in the endocrine system are due to a fundamental cellular defect in the diabetic syndrome. A complex, long-term metabolic condition called diabetes mellitus causes increased blood glucose levels as a result of insufficient insulin synthesis or uptake. The goal of this review article is to give a thorough overview of the complex interactions between the endocrine system and diabetes mellitus pathogenesis. It is still unknown how much these endocrine system changes contribute to the vascular pathologies seen in people with diabetes mellitus and whether some of the abnormalities seen in the endocrine system is due to a fundamental cellular defect in the diabetic syndrome. A complex, long-term metabolic condition called diabetes mellitus causes increased blood glucose levels as a result of insufficient insulin synthesis or uptake. The goal of this review article is to give a thorough overview of the complex interactions between the endocrine system and diabetes mellitus pathogenesis. It results from dysregulation of the endocrine system, primarily involving the pancreas, and its hormones, particularly insulin and glucagon. This review article provides an in-depth analysis of recent advances in our understanding of the endocrine system’s; role in diabetes mellitus, encompassing both type 1 and type 2 diabetes. The review begins by elucidating the pivotal roles of the endocrine system in maintaining glucose homeostasis, highlighting the pancreas; contribution through the secretion of insulin and glucagon. It explores the etiological factors that underlie diabetes, including genetics, lifestyle, and environmental influences. The article then delves into the pathophysiological mechanisms responsible for the onset and progression of diabetes mellitus, encompassing insulin resistance, β-cell dysfunction, and the involvement of various hormones, cytokines, and adipocytes. A large worldwide health burden is posed by diabetes mellitus, a set of metabolic illnesses characterized by increased blood glucose levels. The endocrine system, which is made up of numerous glands and hormones, is intricately related to the aetiology of diabetes and plays a crucial role in regulating glucose metabolism. The goal of this in-depth review article is to give a complete analysis of the state of knowledge at the moment about how the endocrine system and diabetes mellitus interact. Beginning with a discussion of the physiological part played by the endocrine system in maintaining glucose homeostasis, the overview highlights the important hormones insulin, glucagon, and others as well as the major participants in this process. After that, it explores the complex aetiology of diabetes mellitus, including type 1, type 2, and gestational diabetes, highlighting the role that genetic, environmental, and lifestyle variables have in the progression of the disease. Advancements in the understanding of the endocrine system’s; intricate signalling pathways, including insulin secretion, insulin resistance, and hormonal regulation, are explored in detail.

Micromotor Based Mini-Tablet for Oral Delivery of Insulin.

Diabetes is a metabolic disorder characterized by hyperglycemia due to defective insulin secretion or its biological dysfunction. However, frequent subcutaneous injection of insulin often results in discomfort and local tissue infection. Herein, we demonstrate the successful fabrication of a mini-tablet system based on self-propelled micromotors with biocompatibility and biodegradability for oral colon administration of insulin. The insulin layer is first constructed onto the surface of a magnesium based micromotor via electrostatic interactions, followed by a tableting process. The resulting mini-tablets are then coated with esterified starch with colonic degradation capability, thus achieving controlled release of the embedded micromotors in the colon region. In the meantime, autonomous movement of the released micromotors with a speed up to 76.22 μm·s-1 further results in enhanced colonic uptake and absorption of insulin, realizing long-term control of blood glucose for more than 5 h. Our micromotor based mini-tablet system can not only broaden the biomedical applications of emerging self-propelled micromotors but also offer an appealing strategy for oral administration of biomacromolecular drugs represented by insulin.

Design and development of chitosan-insulin-transfersomes (Transfersulin) as effective intranasal nanovesicles for the treatment of Alzheimer’s disease: In vitro, in vivo, and ex vivo evaluations

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).