Dynamic diabetes solutions: physiologic insulin resensitization

2021 ◽  
Vol 6 (8) ◽  
Keyword(s):  
Insulin Resistance ◽  
Diabetic Complications ◽  
Exogenous Insulin ◽  
Lifestyle Modifications ◽  
Disease Treatment ◽  
Standard Drug ◽  
Rest Periods ◽  
Oscillatory Pattern ◽  
Treatment Of Diabetes ◽  
Periodic Cycles

Diabetes is a disease currently affecting over 30 million Americans and is a leading cause of amputation, blindness, and chronic kidney disease. Treatment of diabetes with medications and lifestyle modifications alone have not eliminated these complications, because in part they lack the ability to restore the periodic cycles and rest periods of insulin that exist in healthy physiology. Insulin is excreted in a cyclical and oscillatory pattern by the pancreas, that is critical to maintain adequate insulin sensitivity at the insulin receptor level. Administration of exogenous insulin bio identically matching this physiologic profile is more effective at controlling blood glucose level and reducing complications of diabetes than standard drug therapy and lifestyle modifications alone. This matching of physiological insulin helps reduce inflammatory cascades responsible for a number of diabetic complications. In this article, we will review how insulin is secreted and functions physiologically and highlight a dynamic insulin delivery modality that mimics normal secretion profiles. This biomimicry reduces insulin exposure, which appears to reduce the progression to or worsening of insulin resistance. We will review how administration of insulin in this manner has been associated with reduction of diabetic complications.

Plant Compounds for the Treatment of Diabetes, a Metabolic Disorder: NF-κB as a Therapeutic Target

2020 ◽  
Vol 26 (39) ◽  
pp. 4955-4969
Author(s):  
Ravi Sahukari ◽  
Jyothi Punabaka ◽  
Shanmugam Bhasha ◽  
Venkata S. Ganjikunta ◽  
Shanmugam K. Ramudu ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Current Knowledge ◽  
World Population ◽  
Future Studies ◽  
Expression Of Genes ◽  
Treatment Of Diabetes ◽  
Online Library ◽  
And Oxidative Stress ◽  
Stress Activation ◽  
Plant Compounds

Background: The prevalence of diabetes in the world population hás reached 8.8 % and is expected to rise to 10.4% by 2040. Hence, there is an urgent need for the discovery of drugs against therapeutic targets to sojourn its prevalence. Previous studies proved that NF-κB serves as a central agent in the development of diabetic complications. Objectives: This review intended to list the natural plant compounds that would act as inhibitors of NF-κB signalling in different organs under the diabetic condition with their possible mechanism of action. Methods: Information on NF-κB, diabetes, natural products, and relation in between them, was gathered from scientific literature databases such as Pubmed, Medline, Google scholar, Science Direct, Springer, Wiley online library. Results and Conclusion: NF-κB plays a crucial role in the development of diabetic complications because of its link in the expression of genes that are responsible for organs damage such as kidney, brain, eye, liver, heart, muscle, endothelium, adipose tissue and pancreas by inflammation, apoptosis and oxidative stress. Activation of PPAR-α, SIRT3/1, and FXR through many cascades by plant compounds such as terpenoids, iridoids, flavonoids, alkaloids, phenols, tannins, carbohydrates, and phytocannabinoids recovers diabetic complications. These compounds also exhibit the prevention of NF-κB translocation into the nucleus by inhibiting NF-κB activators, such as VEGFR, RAGE and TLR4 receptors, which in turn, prevent the activation of many genes involved in tissue damage. Current knowledge on the treatment of diabetes by targeting NF-κB is limited, so future studies would enlighten accordingly.

Berberine in the treatment of diabetes mellitus: a review

2020 ◽  
Vol 20 ◽  
Author(s):  
Aleksandra Baska ◽  
Kamil Leis ◽  
Przemysław Gałązka
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Intestinal Flora ◽  
Glucose Absorption ◽  
Hepatocyte Nuclear Factor ◽  
Peripheral Tissues ◽  
Macrophages Polarization ◽  
Treatment Of Diabetes ◽  
Hepatocyte Nuclear Factor 4

: Berberine is an alkaloid found in plants. It has e.g. neuroprotective, anti-inflammatory and hypolipidemic activity. The research proves that it also strongly impacts the carbohydrate metabolism. The compound also protects pancreatic βcells and increases sensitivity to insulin in peripheral tissues via the induction of GLUT-1, GLUT-4 and insulin type 1 (Ins1) receptors activity. It also stimulates glycolysis and leads to a decrease in insulin resistance by macrophages polarization, lipolytic processes induction and energy expenditure enhancement (by reducing body mass and limiting insulin resistance caused by obesity). In liver berberine inhibits FOX01, SREBP1 and ChREBP pathways, and HNF-4α (hepatocyte nuclear factor 4 alpha) mRNA that hinder gluconeogenesis processes. In intestines it blocks α-glucosidase contributing to glucose absorption decrease. Its interference in intestinal flora reduces levels of monosaccharides and suppresses diabetes mellitus complications development.

scholarly journals Targeting mitochondrial biogenesis: a potential approach for preventing and controlling diabetes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ritika Singh ◽  
Lucy Mohapatra ◽  
Alok Shiomurthi Tripathi
Keyword(s):  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Mitochondrial Biogenesis ◽  
Diabetic Complications ◽  
Reactive Oxygen ◽  
Main Body ◽  
Oxygen Species ◽  
Treatment And Prevention ◽  
Skeletal Muscle Insulin Resistance ◽  
Mitochondrial Number

Abstract Background Diabetes mellitus is a lingering hyperglycemic ailment resulting in several life-threatening difficulties. Enduring hyperglycemia often persuades the buildup of reactive oxygen species that are the significant pathological makers of diabetic complications. The mitochondrial dysfunction, with mitochondrial damage and too much production of reactive oxygen species, have been proposed to be convoluted in the progress of insulin resistance. Numerous studies advocate that agents that enhance the mitochondrial number and/or decrease their dysfunction, could be greatly helpful in management of diabetes and its complications. Main body Mitochondrial biogenesis is an extremely delimited procedure arbitrated by numerous transcription influences, in which mitochondrial fusion and fission happen in synchronization in a standard vigorous cell. But this synchronization is greatly disturbed in diabetic condition designated by modification in the working of several important transcription factors regulating the expressions of different genes. Numerous preclinical and clinical investigations have suggested that, the compromised functions of mitochondria play a significant protagonist in development of pancreatic β-cell dysfunction, skeletal muscle insulin resistance and several diabetic complications. However, there are several phytoconstituents performing through numerous alleyways, either unswervingly by motivating biogenesis or indirectly by constraining or averting dysfunction and producing a beneficial effect on overall function of the mitochondria. Conclusion This review describes standard mitochondrial physiology and anomalous modifications that transpire in answer to persistent hyperglycemia in diabetes condition. It also discusses about the different phytoconstituents that can affect the biogenesis pathways of mitochondria and thus can be used in the treatment and prevention of diabetes.

scholarly journals AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation

2022 ◽  
Vol 146 ◽  
pp. 112563
Author(s):  
Maliheh Entezari ◽  
Danial Hashemi ◽  
Afshin Taheriazam ◽  
Amirhossein Zabolian ◽  
Shima Mohammadi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Diabetic Complications ◽  
Clinical Investigation ◽  
Ampk Signaling

scholarly journals Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy)

2022 ◽  
pp. 1-8
Author(s):  
Maegan L. Watson-Skaggs ◽  
Tracy L. Gieger ◽  
Hiroto Yoshikawa ◽  
Michael W. Nolan
Keyword(s):  
Insulin Resistance ◽  
Overall Survival ◽  
Adverse Effects ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Insulin Dose ◽  
Exogenous Insulin ◽  
Endocrine Response ◽  
Overall Survival Time ◽  
Insulin Requirements

Abstract OBJECTIVE To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS 14 client-owned cats. PROCEDURES Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

A Correlational Study of Hepatic Steatosis (Fatty Liver Disease) and Liver Enzymes (ALT, AST, GGT) In The Scenario of Insulin Resistance Among Young Medicos.

2021 ◽  
Vol 17 (4) ◽  
pp. 717-725
Author(s):  
Samarpita Mukherjee ◽  
Shubhrajit Saha ◽  
Ushasi Banerjee ◽  
Arup Kumar Banerjee ◽  
Ritam Banerjee
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Lifestyle Modifications ◽  
Cross Sectional ◽  
Mean Values ◽  
Nonalcoholic Fatty Liver ◽  
Study Population

Background and Objectives In the last few decades,Nonalcoholic Fatty Liver Disease (NAFLD) has become a common health issue that leads to serious complications like cirrhosis, cardiovascular disease, etc. Insulin resistance (IR) is the key pathogenic factor for NAFLD. The young medicos being habituated in stressful and sedentary lifestyle and representative of the youth as well can fully justify their selection as study population and help to build social awareness by emphasizing the importance of early lifestyle modifications in preventing or delaying the severe complications of NAFLD. This study is aiming to find out if there is any correlation of hepatic steatosis with IR, Alanine Transaminases (ALT), Aspartate Transaminases (AST) or Gama Glutamyl Transferases (GGT) and also to identify if one enzyme is better correlating with hepatic steatosis than others in the scenario of Insulin Resistance among young medicos. METHODS: 132 medical students of North Bengal Medical College, aged between 18-25 years were included in this institution based observational cross-sectional study. Their Fasting Insulin, glucose, ALT, AST, GGT were measured, and IR was calculated by the Homeostatic Assessment of Insulin Resistance (HOMA-IR) calculator. Sonography was done to assess Hepatic steatosis. RESULTS: Among 132 subjects normal, grade 1 and grade 2 fatty changes have been found in 67.4%, 25%, and 7.6% of the study population respectively. The Grouping was done using the cut-off value of IR (i.e. subjects with IR<1.525 vs. IR≥1.525). Significant differences were found in the mean values of ALT, AST, GGT between groups. Significant positive concordances were found between enzymes ALT, GGT, and hepatic steatosis in subjects having IR ≥ 1.525.Regression analysis showed that higher GGT values have a stronger positive correlation with hepatic steatosis than ALT among the same. Interpretation and Conclusion From this study, we can interpret that subjects having higher GGT values are better associated with steatosis than those having higher ALT values and can lead us to the conclusion that GGT might be an important independent marker for NAFLD associated with IR. Furthermore, such observations may suggest considering GGT as a marker for assessing the severity of fatty liver irrespective of etiopathogenesis, though the population-based vivid evaluation is highly recommended.

Genetics of severe insulin resistance

2011 ◽  
pp. 1759-1764
Author(s):  
Robert K. Semple ◽  
David B. Savage ◽  
Stephen O’Rahilly
Keyword(s):  
Insulin Resistance ◽  
Insulin Signalling ◽  
Single Gene ◽  
Clinical History ◽  
Insulin Requirement ◽  
Exogenous Insulin ◽  
Oral Glucose Tolerance Testing ◽  
Severe Insulin Resistance ◽  
Diagnostic Thresholds ◽  
Normal Ranges

As the prevalence of obesity burgeons, so the prevalence of insulin resistance follows. A small minority of patients have severe insulin resistance without obesity. These patients, while not contributing significantly to the general prevalence of diabetes, often harbour pathogenic single gene defects affecting insulin signalling or adipose tissue function. Clinical history and examination may offer strong clues to the presence of severe insulin resistance, but laboratory confirmation should usually be sought. Biochemical diagnostic thresholds for severe insulin resistance are arbitrary, and should, ideally, be defined relative to BMI-adjusted population normal ranges (Fig. 13.3.5.1). However, one set of approximate diagnostic criteria is as follows: ◆ non-diabetic and BMI under 30 kg/m2—fasting insulin above 150 pmol/l OR peak insulin on oral glucose tolerance testing above 1500 pmol/l ◆ absolute insulin deficiency and BMI under 30 kg/m2—exogenous insulin requirement above 3 U/kg/day ◆ partial β‎ cell decompensation and/or BMI over 30 kg/m2—insulin levels are difficult to interpret in the context of obesity, while, in diabetes, glucotoxicity, impaired islet function, and a combination of endogenous and exogenous insulin in the circulation confuse the biochemical picture. In this setting, the clinical history and features such as acanthosis nigricans assume particular importance in making a diagnosis of likely monogenic severe insulin resistance, with subjective clinical judgement often required.

scholarly journals Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

2020 ◽  
Vol 21 (14) ◽  
pp. 5163 ◽  
Author(s):  
Wei Hu ◽  
Xiang Song ◽  
Haibo Yu ◽  
Jingyu Sun ◽  
Yong Zhao
Keyword(s):  
Extracellular Vesicles ◽  
Diabetic Complications ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Future Research ◽  
Cell Based Therapy ◽  
Liver And Kidney ◽  
Life Threatening ◽  
Treatment Of Diabetes

Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.

scholarly journals Electronic Cigarette Use and Metabolic Syndrome Development: A Critical Review

Toxics ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 105
Author(s):  
Ilona Górna ◽  
Marta Napierala ◽  
Ewa Florek
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Arterial Blood Pressure ◽  
Abdominal Obesity ◽  
Critical Review ◽  
Lifestyle Modifications ◽  
The Metabolic Syndrome ◽  
Arterial Blood ◽  
The Impact

The metabolic syndrome is a combination of several metabolic disorders, such as cardiovascular disease, atherosclerosis, and type 2 diabetes. Lifestyle modifications, including quitting smoking, are recommended to reduce the risk of metabolic syndrome and its associated complications. Not much research has been conducted in the field of e-cigarettes and the risk of metabolic syndrome. Furthermore, taking into account the influence of e-cigarettes vaping on the individual components of metabolic syndrome, i.e, abdominal obesity, insulin resistance, dyslipidemia and elevated arterial blood pressure, the results are also ambiguous. This article is a review and summary of existing reports on the impact of e-cigarettes on the development of metabolic syndrome as well as its individual components. A critical review for English language articles published until 30 June 2020 was made, using a PubMed (including MEDLINE), Cochrane, CINAHL Plus, and Web of Science data. The current research indicated that e-cigarettes use does not affect the development of insulin resistance, but could influence the level of glucose and pre-diabetic state development. The lipid of profile an increase in the TG level was reported, while the influence on the level of concentration of total cholesterol, LDL fraction, and HDL fraction differed. In most cases, e-cigarettes use increased the risk of developing abdominal obesity or higher arterial blood pressure. Further research is required to provide more evidence on this topic.

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