Medical Physiology Commons^™

Mitochondrial Dysfunction: At The Nexus Between Alcohol-Associated Immunometabolic Dysregulation And Tissue Injury, Robert W. Siggins, Patrick M. Mcternan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina

School of Medicine Faculty Publications

Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such as ATP synthesis and initiation of apoptosis. However, current research has provided evidence that mitochondria participate in myriad cellular processes, including immune activation, nutrient sensing in pancreatic β-cells, and skeletal muscle stem and progenitor cell differentiation. The literature indicates that alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation and disrupting mitochondrial dynamics, leading to dysfunctional mitochondria …

Olive Oil Diet In Mild Pre-Gestational Diabetes Impacts Offspring Β-Cell Development., Bushra Taqui, Farsad Asadi, Evangelina Capobianco, Daniel Barry Hardy, Alicia Jawerbaum, Edith Juliana Arany

Physiology and Pharmacology Publications

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect …

Maternal Exposure To Δ9-Tetrahydrocannabinol Impairs Female Offspring Glucose Homeostasis And Endocrine Pancreatic Development In The Rat., Ryan Gillies, Kendrick Lee, Sebastian Vanin, Steven R Laviolette, Alison C Holloway, Edith Arany, Daniel B Hardy

Physiology and Pharmacology Publications

Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy will impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months …

Maternal Exposure To Δ9-Tetrahydrocannabinol Impairs Female Offspring Glucose Homeostasis And Endocrine Pancreatic Development In The Rat., Ryan Gillies, Kendrick Lee, Sebastian Vanin, Steven R Laviolette, Alison C Holloway, Edith Arany, Daniel B Hardy

Physiology and Pharmacology Publications

Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy would impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

Effects Of Protein Deficiency On Perinatal And Postnatal Health Outcomes, Shelby L. Oke, Daniel B. Hardy

Physiology and Pharmacology Publications

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads …

Uptake, Storage And Secretion Of 5-Hydroxytryptamine And Its Amino Acid Precursor By Dispersed Rat Pancreas Acinar Cells, Ligia Stern, A. Tenenhouse, E. Yu

Edward Yu

Rat pancreas acinar cells contain 5-hydroxytryptamine (5-HT; 10.86 +/- 2.52 ng/i.u. amylase), all of which can be accounted for by the 5-HT recovered from the zymogen granule fraction of these cells (10.70 +/- 3.06 ng/i.u. amylase). When incubated with [14C]5-HT dispersed acinar cells take up the amine and concentrate it in zymogen granules. These cells will also take up [14C]5-HTP (5-hydroxytryptophan), decarboxylate it and store the [14C]5-HT so produced in zymogen granules. 5-HTP itself is not taken up by the granules. 5-HT is incorporated into zymogen granules early in their formation; no amine is accumulated by mature zymogen granules and …