L-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to Intermittent Hypoxia.

Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated.

L-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to Intermittent Hypoxia.

Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated.

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity.

Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity.

Defining the Role of mTORC1 in Thyrocytes by Studying the TSC2 Conditional Knockout Mouse Model.

The thyroid gland is susceptible to abnormal epithelial cell growth, often resulting in thyroid dysfunction. The serine-threonine protein kinase mechanistic target of rapamycin (mTOR) regulates cellular metabolism, proliferation, and growth through two different protein complexes, mTORC1 and mTORC2. The PI3K-Akt-mTORC1 pathway's overactivity is well associated with heightened aggressiveness in thyroid cancer, but recent studies indicate the involvement of mTORC2 as well.

Predictors of lack of glycemic control in persons with type 2 diabetes.

Background: Professional guidelines recommend an HbA1c < 7% for most people with diabetes and < 8.5% for those with relaxed glycemic goals. However, many people with type 2 diabetes mellitus (T2DM) are unable to achieve the desired HbA1c goal.

Unbiased Phosphoproteome Mining Reveals New Functional Sites of Metabolite-Derived PTMs Involved in MASLD Development.

Post-translational modifications (PTMs) of proteins are paramount in health and disease. Phosphoproteome analysis by enrichment techniques is becoming increasingly attractive for biomedical research. Recent findings show co-enrichment of other phosphate-containing biologically relevant PTMs, but these results were obtained by closed searches focused on the modifications sought.

Sex Differences in Pancreatic β-Cell Physiology and Glucose Homeostasis in C57BL/6J Mice.

The importance of sexual dimorphism has been highlighted in recent years since the National Institutes of Health's mandate on considering sex as a biological variable. Although recent studies have taken strides to study both sexes side by side, investigations into the normal physiological differences between males and females are limited. In this study, we aimed to characterized sex-dependent differences in glucose metabolism and pancreatic β-cell physiology in normal conditions using C57BL/6J mice, the most common mouse strain used in metabolic studies.

Comparison of Glycemic Control Between In-Person and Virtual Diabetes Consults in Hospitalized Patients With Diabetes.

Background: There is limited evidence that the diabetes in-person consult in hospitalized patients can be replaced by a virtual consult. During COVID-19 pandemic, the diabetes in-person consult service at the University of Miami and Miami Veterans Affairs Healthcare System transitioned to a virtual model. The aim of this study was to assess the impact of telemedicine on glycemic control after this transition.

Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production.

Aim/hypothesis: Hyperglycaemia is associated with alpha cell dysfunction, leading to dysregulated glucagon secretion in type 1 and type 2 diabetes; however, the mechanisms involved are still elusive. The nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) plays a major role in the maintenance of alpha cell mass and function. We studied the regulation of alpha cell mTORC1 by nutrients and its role in the development of hyperglucagonaemia in diabetes.

Connecting From Afar: Implementation of Remote Data-Sharing for Patients With Type 1 Diabetes on Insulin Pump Therapy.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of .

Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice.

Objective: The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of β-cells to insulin resistant state.

Method: Here, we use mice with heterozygous deletion of raptor in β-cells (βra) to assess whether reduced mTORC1 function is critical for β-cell function in normal conditions or during β-cell adaptation to high-fat diet (HFD).

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells.

Time-dependent effects of endogenous hyperglucagonemia on glucose homeostasis and hepatic glucagon action.

Elevation of glucagon levels and increase in α cell proliferation is associated with states of hyperglycemia in diabetes. A better understanding of the molecular mechanisms governing glucagon secretion could have major implications for understanding abnormal responses to hypoglycemia in patients with diabetes and provide novel avenues for diabetes management. Using mice with inducible induction of Rheb1 in α cells (αRhebTg mice), we showed that short-term activation of mTORC1 signaling is sufficient to induce hyperglucagonemia through increased glucagon secretion.

Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition.

Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of the metabolic alterations that occur in different organs in diabetes and in response to SGLT2i.

Medicaid insured persons with diabetes have increased proportion of missed appointments and high HbA1c.

Objective: This study was conducted to evaluate whether the type of insurance coverage is associated with missed appointments and to evaluate the effect of missed appointments on diabetes control.

Methods: All patients with diabetes mellitus (DM) managed at a major academic medical center between Jan 2015 and Dec 2020 were included in analysis. Association between insurance coverage and the proportion of missed appointments was evaluated with adjustments for demographic variables and social determinants of health.

Novel roles of mTORC2 in regulation of insulin secretion by actin filament remodeling.

Mammalian target of rapamycin (mTOR) kinase is an essential hub where nutrients and growth factors converge to control cellular metabolism. mTOR interacts with different accessory proteins to form complexes 1 and 2 (mTORC), and each complex has different intracellular targets. Although mTORC1's role in β-cells has been extensively studied, less is known about mTORC2's function in β-cells.

The Transcription Factor YY1 Is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-Cells.

Identifying the mechanisms behind the β-cell adaptation to failure is important to develop strategies to manage type 2 diabetes (T2D). Using db/db mice at early stages of the disease process, we took advantage of unbiased RNA sequencing to identify genes/pathways regulated by insulin resistance in β-cells. We demonstrate herein that islets from 4-week-old nonobese and nondiabetic leptin receptor-deficient db/db mice exhibited downregulation of several genes involved in cell cycle regulation and DNA repair.

Maternal High-Fat Diet During Pre-Conception and Gestation Predisposes Adult Female Offspring to Metabolic Dysfunction in Mice.

The risk of obesity in adulthood is subject to programming in the womb. Maternal obesity contributes to programming of obesity and metabolic disease risk in the adult offspring. With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of maternal high-fat diet (HFD) during pregnancy on offspring's metabolic heath trajectory.

Trimethylguanosine synthase 1 is a novel regulator of pancreatic beta-cell mass and function.

Type 2 diabetes is a metabolic disorder associated with abnormal glucose homeostasis and is characterized by intrinsic defects in β-cell function and mass. Trimethylguanosine synthase 1 (TGS1) is an evolutionarily conserved enzyme that methylates small nuclear and nucleolar RNAs and that is involved in pre-mRNA splicing, transcription, and ribosome production. However, the role of TGS1 in β-cells and glucose homeostasis had not been explored.