Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats.

Objective: Post-bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication.

Metabolic comparison of one-anastomosis gastric bypass, single-anastomosis duodenal-switch, Roux-en-Y gastric bypass, and vertical sleeve gastrectomy in rat.

Background: One-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal switch (SADS) have become increasingly popular weight loss strategies. However, data directly comparing the effectiveness of these procedures with Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (SG) are limited.

Objectives: To examine the metabolic outcomes of OAGB, SADS, RYGB, and SG in a controlled rodent model.

Targeting FXR and FGF19 to Treat Metabolic Diseases-Lessons Learned From Bariatric Surgery.

Bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective interventions available for sustained weight loss and improved glucose metabolism. Bariatric surgery alters the enterohepatic bile acid circulation, resulting in increased plasma bile levels as well as altered bile acid composition. While it remains unclear why both VSG and RYGB can alter bile acids, it is possible that these changes are important mediators of the effects of surgery.

Specific subpopulations of hypothalamic leptin receptor-expressing neurons mediate the effects of early developmental leptin receptor deletion on energy balance.

Objective: To date, early developmental ablation of leptin receptor (LepRb) expression from circumscribed populations of hypothalamic neurons (e.g., arcuate nucleus (ARC) Pomc- or Agrp-expressing cells) has only minimally affected energy balance.

Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion.

Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, the mechanisms responsible for the regulation of pancreatic α cell mass and function are not completely understood. In the current study, we identified mTOR complex 1 (mTORC1) as a major regulator of α cell mass and glucagon secretion.

Loss of mTORC1 signalling impairs β-cell homeostasis and insulin processing.

Deregulation of mTOR complex 1 (mTORC1) signalling increases the risk for metabolic diseases, including type 2 diabetes. Here we show that β-cell-specific loss of mTORC1 causes diabetes and β-cell failure due to defects in proliferation, autophagy, apoptosis and insulin secretion by using mice with conditional (βraKO) and inducible (MIP-βraKO) raptor deletion. Through genetic reconstitution of mTORC1 downstream targets, we identify mTORC1/S6K pathway as the mechanism by which mTORC1 regulates β-cell apoptosis, size and autophagy, whereas mTORC1/4E-BP2-eIF4E pathway regulates β-cell proliferation.

Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation.

Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However, interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent.

Overexpression of Kinase-Dead mTOR Impairs Glucose Homeostasis by Regulating Insulin Secretion and Not β-Cell Mass.

Regulation of glucose homeostasis by insulin depends on β-cell growth and function. Nutrients and growth factor stimuli converge on the conserved protein kinase mechanistic target of rapamycin (mTOR), existing in two complexes, mTORC1 and mTORC2. To understand the functional relevance of mTOR enzymatic activity in β-cell development and glucose homeostasis, we generated mice overexpressing either one or two copies of a kinase-dead mTOR mutant (KD-mTOR) transgene exclusively in β-cells.

Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure.

Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure.

Original research in the classroom: why do zebrafish spawn in the morning?

As part of an upper level undergraduate developmental biology course at the University of Minnesota Duluth, we developed a unit in which students carried out original research as part of a cooperative class project. Students had the opportunity to gain experience in the scientific method from experimental design all of the way through to the preparation of publication on their research that included text, figures, and tables. This kind of inquiry-based learning has been shown to have many benefits for students, including increased long-term learning and a better understanding of the process of scientific discovery.

Chronic placental ischemia alters amniotic fluid milieu and results in impaired glucose tolerance, insulin resistance and hyperleptinemia in young rats.

Although small size at birth is associated with hypertension and associated co-morbidities such as insulin resistance and type II diabetes mellitus, many of the animal models employed to simulate this phenomenon do not closely mimic the ontogeny of growth restriction observed clinically. While intrauterine growth restriction (IUGR) is often detected near mid-pregnancy in women and persists until term, most rodent models of IUGR employ ligation of uterine arteries for a brief period during late gestation (days 19-21 of pregnancy). We hypothesized that IUGR associated with chronic reduction in uteroplacental perfusion (RUPP) and placental ischemia during the third trimester of pregnancy in the rat alters the amniotic fluid (AF) environment and results in hypertensive offspring presenting with metabolic abnormalities such as glucose intolerance and insulin resistance.