Michigan Medicine’s Post

#diabetes #cells #biology #medicine #medicalsciences #healthcare https://lnkd.in/g7pffYxk Summary Type 1 diabetes (T1D) is widely considered to result from the #autoimmune destruction of insulin-producing β cells. This concept has been a central tenet for decades of attempts seeking to decipher the disorder’s pathogenesis and prevent/reverse the disease. Recently, this and many other disease-related notions have come under increasing question, particularly given knowledge gained from analyses of human T1D pancreas. Perhaps most crucial are findings suggesting that a collective of cellular constituents—immune, endocrine, and exocrine in origin—mechanistically coalesce to facilitate T1D. This review considers these emerging concepts, from basic science to clinical research, and identifies several key remaining knowledge voids.

New study in Diabetes, Obesity, and Metabolism compares SGLT2 inhibitors with DPP-4 inhibitors and sulfonylureas in Type 2 diabetes patients with peripheral artery disease. Results show lower risk for lower extremity amputation with SGLT2 inhibitors vs DPP-4 inhibitors and higher risk vs sulfonylureas. Important insights for clinical practice. #diabetes #research #clinicalpractice #SGLT2inhibitors

🌟 Efficacy and Safety of SGLT2 Inhibitors With and Without GLP-1 Receptor Agonists 🌟 A recent meta-analysis published in The Lancet Diabetes & Endocrinology explores the efficacy and safety of SGLT2 inhibitors, with or without GLP-1 receptor agonists (GLP-1 RAs). The results are promising for patients with diabetes, cardiovascular, and kidney conditions. 🔍 Case Study: Patient Profile: Name: David Age: 60 Diagnosis: Type 2 Diabetes with Cardiovascular Disease Current Treatment: SGLT2 inhibitor + GLP-1 RA Outcome: Reduced risk of major adverse cardiovascular events (MACE) Decreased hospitalizations for heart failure Slowed progression of chronic kidney disease Discussion Questions: What are the main benefits of combining SGLT2 inhibitors with GLP-1 RAs in managing type 2 diabetes? How do SGLT2 inhibitors improve cardiovascular outcomes in patients with diabetes? What considerations should be made when prescribing these medications together? Interactive Q&A: Q1: How do SGLT2 inhibitors reduce the risk of major adverse cardiovascular events (MACE)? A1: SGLT2 inhibitors reduce MACE by improving glycemic control, lowering blood pressure, and promoting natriuresis, which collectively reduce cardiovascular stress. Q2: Are there any specific patient populations that benefit the most from the combination of SGLT2 inhibitors and GLP-1 RAs? A2: Patients with type 2 diabetes who have a high risk of cardiovascular disease or existing cardiovascular conditions benefit significantly from this combination therapy. Poll: Which outcome is most important to you when choosing a diabetes medication? Cardiovascular protection Kidney health Blood sugar control Weight management Call to Action: 🔗 Learn more about the study here and join our live Q&A session with Dr. Priyadarshini Balasubramanian on the benefits of SGLT2 inhibitors and GLP-1 RAs in diabetes management. Don’t miss this opportunity to get your questions answered! #DiabetesManagement #SGLT2Inhibitors #GLP1RAs #CardiovascularHealth #KidneyHealth #TheLancet #MedicalResearch #Endocrinology #PatientCare References: Priyadarshini Balasubramanian, MD. "Efficacy and Safety of SGLT2 Inhibitors With and Without GLP-1 Receptor Agonists." The Lancet Diabetes & Endocrinology. Stay informed and be part of the conversation! 🌐

The article by Rohbeck et al. (2021), titled "Cannabinoid Receptor-Mediated Metabolic Regulation and Diabetes," delves into the complex interplay between the endocannabinoid system (ECS), metabolic regulation, and the pathology of diabetes. The ECS, which includes cannabinoid receptors CB1 and CB2, along with endogenous cannabinoids, plays a pivotal role in managing various metabolic processes such as energy homeostasis, glucose metabolism, and lipid storage. 𝗞𝗲𝘆 𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀 𝗳𝗿𝗼𝗺 𝘁𝗵𝗲 𝗦𝘁𝘂𝗱𝘆: 𝗖𝗕𝟭 𝗥𝗲𝗰𝗲𝗽𝘁𝗼𝗿: The CB1 receptor is predominantly found in the central nervous system (CNS) but also in peripheral tissues, where it influences energy storage and stimulates appetite. In metabolic conditions such as type 2 diabetes, CB1 overactivation is associated with impaired glucose metabolism. This contributes to dyslipidemia, weight gain, and a worsened insulin response, all of which drive the onset and progression of diabetes. 𝗖𝗕𝟮 𝗥𝗲𝗰𝗲𝗽𝘁𝗼𝗿:  Unlike CB1, CB2 receptors are primarily found in immune cells and play a vital role in controlling inflammation. In metabolic disorders like diabetes, chronic low-grade inflammation is a key driver of insulin resistance and tissue dysfunction. The study highlights that CB2 activation can reduce pro-inflammatory markers, presenting a possible therapeutic avenue for improving insulin sensitivity and reducing the inflammatory burden seen in diabetes. 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗜𝗺𝗽𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀: 𝗖𝗕𝟭 𝗜𝗻𝗵𝗶𝗯𝗶𝘁𝗶𝗼𝗻: Medications that targeted the CB1 receptor ( rimonabant) had shown promising results in weight loss and metabolic improvements. However, despite these benefits, serious psychiatric side effects (such as anxiety and depression) limited its use in clinical practice so it was withdrawn from the market. Thus, future therapies must focus on creating safer, more selective inhibitors that avoid such risks. 𝗖𝗕𝟮 𝗔𝗰𝘁𝗶𝘃𝗮𝘁𝗶𝗼𝗻: Conversely, targeting CB2 receptors offers a different approach—by harnessing its anti-inflammatory properties without the psychiatric side effects. This opens up exciting opportunities for metabolic regulation by reducing inflammation-related complications in diabetes and promoting better glucose control. Rohbeck E, Eckel J, Romacho T. Cannabinoid Receptors in Metabolic Regulation and Diabetes. Physiology (Bethesda). 2021 Mar 1;36(2):102-113. doi: 10.1152/physiol.00029.2020

Iron Metabolism and Inflammatory Factors in Renal Dysfunction Patients Chronic kidney disease (CKD) is a major global health issue, affecting an estimated 850 million people worldwide. Its prevalence is rising, making it one of the most common diseases globally. CKD, defined by persistent renal damage for over three months or a glomerular filtration rate (GFR) below 60 mL/min/1.73 m² for a similar duration, was first outlined by the Kidney Disease Outcomes Quality Initiative (KDOQI) in 2002 and later updated by the Kidney Disease Improving Global Outcomes (KDIGO). The causes of CKD are diverse, including diabetes, hypertension, chronic glomerulonephritis, genetic disorders, chronic pyelonephritis, autoimmune diseases, polycystic kidney disease, and medication-induced damage. As CKD advances, it leads to the accumulation of metabolic byproducts typically excreted by the kidneys, causing further damage to various organs and tissues. Progression of CKD ultimately results in end-stage kidney disease (ESKD), requiring interventions such as hemodialysis or kidney transplantation. CKD also increases the risk of cardiovascular events (CVE), often leading to heart failure. Cardiovascular complications are the leading cause of death in CKD patients, frequently occurring before the onset of ESKD. Additionally, CKD-associated anemia is linked to reduced quality of life (QOL), increased hospitalizations, cognitive impairments, and higher mortality risk. Chronic kidney disease (CKD) affects approximately 850 million people worldwide, posing significant healthcare challenges due to complications such as renal anemia, end-stage kidney disease, and cardiovascular diseases. This review examines the complex interactions between iron metabolism, inflammation, and renal dysfunction in CKD. Renal anemia, common in CKD, primarily results from reduced erythropoietin (EPO) production and iron dysregulation, worsening as the disease progresses. Both functional and absolute iron deficiencies, caused by impaired absorption and chronic inflammation, are major contributors to decreased erythropoiesis. A key feature of CKD is the buildup of uremic toxins, such as indoxyl sulfate (IS), which impair iron metabolism and exacerbate anemia. These toxins directly impact renal EPO synthesis and contribute to renal hypoxia, playing a critical role in the pathophysiology of renal anemia. Inflammatory cytokines, especially TNF-α and IL-6, further accelerate CKD progression and disrupt iron homeostasis, thereby increasing anemia severity. Treatment strategies have evolved to address both iron and EPO deficiencies, with new therapies targeting hepcidin and using hypoxia-inducible factor (HIF) stabilizers showing promise. This review highlights the importance of integrated treatment strategies in CKD, focusing on the intricate relationship between iron metabolism, inflammation, and renal dysfunction to improve patient outcomes. #healthcare #CKD #anemia #EPO #HIF #QOL #CVE

Sharing with you my lab latest publication ! Pancreatic β-cells rely to a great degree on their endoplasmic reticulum (ER) to overcome the increased secretary need for insulin biosynthesis and secretion in response to nutrient demand to maintain glucose homeostasis in the body. As a result, β-cells are potentially under ER stress following circulating nutrient levels rise for a proper pro-insulin folding mediated by the unfolded protein response (UPR), underscoring the importance of this process to maintain ER homeostasis for normal β-cell function. However, excessive or prolonged increased influx of nascent pro-insulin into the ER lumen can exceed the ER capacity leading to pancreatic β-cells ER stress and subsequently to β-cell dysfunction. In mammalian cells, an increasing number of evidence suggests that unresolved ER stress signaling pathways play a pivotal role in β-cell failure leading to insulin secretion defect and diabetes. In this review we first summarize recent insights on the role of ER stress and its associated signaling mechanisms on β-cell function and diabetes and second how the ER stress pathways could be targeted during in vitro direct differentiation protocols for generation of hPSC-derived pancreatic β-cells to faithfully phenocopy all features of bona fide human β-cells for diabetes therapy and/or drug screening. #stemcells #insulin #betacells #celltherapy For the full article:

Lipid Function in Health and Disease Lipids play a fundamental role in both health and disease. As essential biomolecules, they perform a variety of critical functions in the body, including energy storage, cell membrane structure, and signal transduction. Lipids are the primary energy source, stored in adipose tissue in the form of triglycerides and mobilized when needed. In cell membranes, lipids such as phospholipids and cholesterol contribute to membrane fluidity, integrity, and functionality, influencing processes such as nutrient transport and cell signaling. In addition to their structural roles, lipids also act as signaling molecules. For example, phosphoinositides and sphingolipids regulate various cellular processes, including cell growth, survival, and apoptosis, while fatty acid-derived eicosanoids play a key role in inflammation and immune responses. Disturbances in lipid metabolism or function can lead to a variety of diseases. In conditions such as obesity and type 2 diabetes, excessive lipid accumulation, especially triglycerides, leads to insulin resistance, which results in metabolic dysfunction. Cardiovascular disease is often caused by an imbalance in lipid metabolism, where high levels of low-density lipoprotein (LDL) and low levels of high-density lipoprotein (HDL) lead to the accumulation of arterial plaques, which can lead to atherosclerosis. In neurological diseases, altered lipid metabolism can impair brain function, such as in diseases such as Alzheimer's disease, where dysregulation of cholesterol and sphingolipids affects neuronal signaling. In addition, lipid imbalance has been implicated in cancer, where aberrant lipid signaling pathways promote tumor growth and metastasis. Therefore, understanding lipid function is crucial to explore the molecular mechanisms behind various diseases, providing opportunities for therapeutic interventions targeting lipid metabolism. References [1] Armella Zadoorian et al., Nature Reviews Endocrinology 2023 (https://lnkd.in/ei-qffJF) [2] Zhongyang Zhang et al., Lipids in Health and Disease 2024 (https://lnkd.in/ey5e7WMD)

Proteomics International recently announced the PromarkerD test for predicting renal decline has been tested in patients with type 1 diabetes for the first time, with the groundbreaking study demonstrating high accuracy for predicting chronic kidney disease. The results are a significant advancement and highlights the versatility and robustness of the PromarkerD test, which has been validated for predicting renal decline in type 2 diabetes, at a time when global authorities are continuing to sound the alarm about the economic, social and health impact of the condition. The findings were presented at the recent Australasian Diabetes Conference in Perth and have been accepted for publication in the journal of Clinical Diabetes and Endocrinology. You can read the Medical Forum’s interview with lead author, endocrinologist at Fremantle Hospital and UWA Professor of Medicine, Dr Tim Davis - https://lnkd.in/gT8rHZ55 Read the full announcement here - https://lnkd.in/g2JK344n #ASX #PIQ #diabetes #Type1Diabetes #PromarkerD #EarlyDiseaseDetection #prognostics #diagnostics #DiabeticKidneyDisease #ChronicKidneyDisease #24ADC

#Review Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection by Andrea Rescalli, Elena Mariani, Francesco Cellesi and Pietro Cerveri https://lnkd.in/gKcPRzUK   #MDPI #Diabetes #Biochemical #enzymes #biosensors #sensors #openaccess   #Abstract Diabetes mellitus is a worldwide-spread chronic metabolic disease that occurs when the pancreas fails to produce enough insulin levels or when the body fails to effectively use the secreted pancreatic insulin, eventually resulting in hyperglycemia. Systematic glycemic control is the only procedure at our disposal to prevent diabetes long-term complications such as cardiovascular disorders, kidney diseases, nephropathy, neuropathy, and retinopathy. Glycated albumin (GA) has recently gained more and more attention as a control biomarker thanks to its shorter lifespan and wider reliability compared to glycated hemoglobin (HbA1c), currently the “gold standard” for diabetes screening and monitoring in clinics. Various techniques such as ion exchange, liquid or affinity-based chromatography and immunoassay can be employed to accurately measure GA levels in serum samples; nevertheless, due to the cost of the lab equipment and complexity of the procedures, these methods are not commonly available at clinical sites and are not suitable to home monitoring. The present review describes the most up-to-date advances in the field of glycemic control biomarkers, exploring in particular the GA with a special focus on the recent experimental analysis techniques, using enzymatic and affinity methods. Finally, analysis steps and fundamental reading technologies are integrated into a processing pipeline, paving the way for future point-of-care testing (POCT). In this view, we highlight how this setup might be employed outside a laboratory environment to reduce the time from measurement to clinical decision, and to provide diabetic patients with a brand-new set of tools for glycemic self-monitoring.

𝗥𝗘𝗡𝗜𝗡-𝗔𝗡𝗚𝗜𝗢𝗧𝗘𝗡𝗦𝗜𝗡-𝗔𝗟𝗗𝗢𝗦𝗧𝗘𝗥𝗢𝗡𝗘 𝗦𝗬𝗦𝗧𝗘𝗠 (𝗥𝗔𝗔𝗦) OVERVIEW OF RAAS The RAAS is a hormone system that regulates blood pressure, fluid, and electrolyte balance. It involves a cascade of reactions starting from the kidneys and impacting multiple organ systems: 🔥 Renin Release: The kidneys release renin in response to low blood pressure, low sodium concentration, or sympathetic nervous system activation. 🔥 Angiotensin I Formation: Renin converts angiotensinogen (produced by the liver) into angiotensin I. 🔥 Angiotensin II Formation: Angiotensin I is converted to angiotensin II by the angiotensin-converting enzyme (ACE), primarily in the lungs. 🔥 Effects of Angiotensin II: 🔹 Vasoconstriction: Raises blood pressure by narrowing blood vessels. 🔹 Aldosterone Release: Stimulates the adrenal glands to release aldosterone, promoting sodium and water retention in the kidneys, increasing blood volume and pressure. 🔹 Antidiuretic Hormone (ADH) Release: Stimulates the release of ADH from the pituitary gland, leading to water reabsorption in the kidneys. 🔹 Thirst Stimulation: Promotes thirst sensation, encouraging water intake. CLINICAL SIGNIFICANCE 💡Hypertension: 🔸 Common in dogs and cats, particularly in association with chronic kidney disease (CKD) and hyperthyroidism in cats. 🔸 RAAS inhibitors like ACE inhibitors (enalapril, benazepril) are used to manage hypertension. 💡Heart Failure: 🔸 In conditions like dilated cardiomyopathy (DCM) and congestive heart failure (CHF) in dogs and cats, RAAS activation contributes to fluid retention and increased blood pressure. 🔸 ACE inhibitors and angiotensin II receptor blockers (ARBs) are used to reduce afterload and preload, improving cardiac output and reducing symptoms. 💡 Chronic Kidney Disease (CKD): 🔸 RAAS activation exacerbates kidney damage by promoting glomerular hypertension and proteinuria. 🔸 ACE inhibitors and ARBs are used to slow the progression of CKD by reducing proteinuria and glomerular pressure. 💡 Proteinuria: 🔸 Persistent proteinuria can be a marker of kidney disease. 🔸 RAAS inhibitors help reduce protein loss in the urine by lowering glomerular capillary pressure. THERAPEUTIC AGENTS 💊 ACE Inhibitors: - Enalapril: Commonly used in dogs and cats for heart failure and CKD. - Benazepril: Preferred in cats due to its dual elimination (renal and hepatic). 💊 Angiotensin II Receptor Blockers (ARBs): - Telmisartan: Used in cats for managing hypertension and proteinuria. 💊 Aldosterone Antagonists: - Spironolactone: Used in heart failure to counteract aldosterone's effects, reducing fluid retention and fibrosis. Credit https://lnkd.in/g-qZSuu9