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Hypoglycemia dog insulin

Jason J Winnick, Guillaume Kraft, Justin M Gregory, Dale S Edgerton, Phillip Williams, Ian A Hajizadeh, Maahum Z Kamal, Marta Smith, Ben Farmer, Melanie Scott, Doss Neal, E Patrick Donahue, Eric Allen, Alan D Cherrington
Liver glycogen is important for the counterregulation of hypoglycemia and is reduced in individuals with type 1 diabetes (T1D). Here, we examined the effect of varying hepatic glycogen content on the counterregulatory response to low blood sugar in dogs. During the first 4 hours of each study, hepatic glycogen was increased by augmenting hepatic glucose uptake using hyperglycemia and a low-dose intraportal fructose infusion. After hepatic glycogen levels were increased, animals underwent a 2-hour control period with no fructose infusion followed by a 2-hour hyperinsulinemic/hypoglycemic clamp...
June 1, 2016: Journal of Clinical Investigation
Dana S Hardin, Wesley Anderson, Jennifer Cattet
INTRODUCTION: Hypoglycemia (Hypo) is the most common side effect of insulin therapy in people with type 1 diabetes (T1D). Over time, patients with T1D become unaware of signs and symptoms of Hypo. Hypo unawareness leads to morbidity and mortality. Diabetes alert dogs (DADs) represent a unique way to help patients with Hypo unawareness. Our group has previously presented data in abstract form which demonstrates the sensitivity and specificity of DADS. The purpose of our current study is to expand evaluation of DAD sensitivity and specificity using a method that reduces the possibility of trainer bias...
December 2015: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Osvaldo Manuel Tiscornia, Gustavo Alberto Negri, Graciela Otero, Fabiana Norma López Mingorance, Hipólito Waisman, Patricia Graciela Tiscornia-Wasserman
prevents, in pancreocytes, the evolving of a "supramaximalecbolic-stimulation" process. The PP involvement as a modulating agent of pancreon's reactivity is reflected by the progressive increment of its plasma values in the first week of an evolving AP episode. In the AP associated to a large meal, an overpowering of the pancreon's brake might have a pivotal role. In experimental and clinical chronic alcoholism, a vagal neuropathy of the Pavlov inhibitory fibers that, as a consequence, impairs the pancreon's brake through a depression of PP secretion is at the basis of an enhanced reactivity of the duodeno-pancreatic reflexes...
June 2015: Acta Gastroenterologica Latinoamericana
Federico Fracassi, Sara Corradini, Michaela Hafner, Felicitas S Boretti, Nadia S Sieber-Ruckstuhl, Claudia E Reusch
OBJECTIVE: To investigate the effects of insulin detemir in dogs with diabetes mellitus. DESIGN: Prospective, uncontrolled clinical trial. ANIMALS: 10 client-owned dogs with naturally occurring diabetes mellitus. PROCEDURES: Dogs were treated with insulin detemir SC every 12 hours for 6 months. Follow-up evaluations were done at 1, 2, 4, 12, and 24 weeks and included evaluation of clinical signs and measurement of blood glucose concentration curves and serum fructosamine concentrations...
July 1, 2015: Journal of the American Veterinary Medical Association
Justin M Gregory, Guillaume Kraft, Melanie F Scott, Doss W Neal, Ben Farmer, Marta S Smith, Jon R Hastings, Eric J Allen, E Patrick Donahue, Noelia Rivera, Jason J Winnick, Dale S Edgerton, Erica Nishimura, Christian Fledelius, Christian L Brand, Alan D Cherrington
Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate four times of basal. In protocol 1, a full counterregulatory response was allowed, whereas in protocol 2, glucagon was fixed at basal, mimicking the diminished α-cell response to hypoglycemia seen in T1DM...
October 2015: Diabetes
Mark Tirmenstein, Joseph Horvath, Michael Graziano, Raja Mangipudy, Thomas Dorr, Karyn Colman, Bradley Zinker, Mark Kirby, Peter T W Cheng, Laura Patrone, John Kozlosky, Timothy P Reilly, Victor Wang, Evan Janovitz
Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and beagle dogs in 1 mo toxicology studies resulted in marked and extended hypoglycemia with associated clinical signs of toxicity and degenerative histopathological changes in the stomach, sciatic nerve, myocardium, and skeletal muscles at exposures comparable to those expected at therapeutic clinical exposures...
August 2015: Toxicologic Pathology
Daniel Howsmon, B Wayne Bequette
Soon after the discovery that insulin regulates blood glucose by Banting and Best in 1922, the symptoms and risks associated with hypoglycemia became widely recognized. This article reviews devices to warn individuals of impending hypo- and hyperglycemia; biosignals used by these devices include electroencephalography, electrocardiography, skin galvanic resistance, diabetes alert dogs, and continuous glucose monitors (CGMs). While systems based on other technology are increasing in performance and decreasing in size, CGM technology remains the best method for both reactive and predictive alarming of hypo- or hyperglycemia...
April 30, 2015: Journal of Diabetes Science and Technology
Chiaki Kuriyama, Jun Zhi Xu, Seunghun Paul Lee, Jenson Qi, Hirotaka Kimata, Tetsuhiro Kakimoto, Keiko Nakayama, Yoshinori Watanabe, Nobuhiko Taniuchi, Kumiko Hikida, Yasuaki Matsushita, Kenji Arakawa, Akira Saito, Kiichiro Ueta, Masaharu Shiotani
Sodium-glucose cotransporter 2 (SGLT2) plays a major role in renal glucose reabsorption. To analyze the potential of insulin-independent blood glucose control, the effects of the novel SGLT2 inhibitor canagliflozin on renal glucose reabsorption and the progression of hyperglycemia were analyzed in Zucker diabetic fatty (ZDF) rats. The transporter activity of recombinant human and rat SGLT2 was inhibited by canagliflozin, with 150- to 12,000-fold selectivity over other glucose transporters. Moreover, in vivo treatment with canagliflozin induced glucosuria in mice, rats, and dogs in a dose-dependent manner...
November 2014: Journal of Pharmacology and Experimental Therapeutics
T Kevin Lee, Caroline Lee, Robert Bischof, Gavin W Lambert, Iain J Clarke, Belinda A Henry
The underlying cause of predisposition to obesity is complex but one marker is cortisol responsiveness. Selection of sheep for high (HR) or low (LR) cortisol responses to adrenocorticotropin shows that HR are more likely to become obese. Increased propensity to obesity is associated with reduced skeletal muscle thermogenesis. We sought to determine whether metabolic or behavioral responses to stress also contribute to altered propensity to obesity in LR and HR. Animals (n=5-10/group) were exposed to 3 stressors and we measured food intake and thermogenesis (recorded with dataloggers implanted into muscle)...
September 2014: Psychoneuroendocrinology
Kensuke Nakamura, Sue-Yee Lim, Kenji Ochiai, Masahiro Yamasaki, Hiroshi Ohta, Keitaro Morishita, Satoshi Takagi, Mitsuyoshi Takiguchi
Abdominal ultrasonography is one of the most common diagnostic imaging modalities used for dogs with suspected insulinoma; however, pancreatic masses are clearly identified in fewer than half of affected dogs and benign pancreatic nodules can be difficult to differentiate from malignant ones. The purpose of this prospective study was to describe contrast-enhanced ultrasonography (CEUS) characteristics of confirmed pancreatic insulinoma in a group of dogs. Inclusion criteria were as follows: (1) repeated hypoglycemia (blood glucose levels <60 mg/dl, twice or more); (2) elevated blood insulin levels with hypoglycemia; (3) pancreatic nodules detected with conventional ultrasonography; and (4) histological confirmation of pancreatic islet cell carcinoma...
January 2015: Veterinary Radiology & Ultrasound
John C Pettersen, John Litchfield, Natasha Neef, Stephen P Schmidt, Norimitsu Shirai, Karen M Walters, Bradley E Enerson, Linda A Chatman, Jeffrey A Pfefferkorn
Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All compounds produced varying degrees of hypoglycemia in all species. Brain neuronal necrosis and/or peripheral neuropathy were observed with most compounds. These findings are consistent with literature reports linking hypoglycemia with nervous system effects...
June 2014: Toxicologic Pathology
R H Unger, L L Madison, W A Muller
The extremely high levels of glucagon recently observed in dogs with severe alloxan-induced diabetes decline promptly and precipitously to normal as soon as exogenous insulin is infused. This suggests that the normal response of the pancreatic alpha cell to hyperglycemia requires the presence of circulating insulin. To determine if the relative hyperglucagonemia of human diabetics responds similarly to insulin repletion, the plasma glucagon response of ten adult-type diabetic patients to a large, predominantly carbohydrate meal was determined with and without the simultaneous forty-five-minute intravenous infusion of glucagon free insulin (0...
May 1972: Diabetes
Kaapjoo Park, Byoung Moon Lee, Kwan Hoon Hyun, Dong Hoon Lee, Hyun Ho Choi, Hyunmi Kim, Wonee Chong, Kyeong Bae Kim, Su Youn Nam
Novel heteroaryl-containing benzamide derivatives were synthesized and screened using an in vitro assay measuring increases in glucose uptake and glucokinase activity stimulated by 10mM glucose in rat hepatocytes. From a library of synthesized compounds, 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methyl pyridin-2-yl)-benzamide (19e) was identified as a potent glucokinase activator with assays demonstrating an EC50 of 315nM and the induction of a 2.23 fold increase in glucose uptake...
April 1, 2014: Bioorganic & Medicinal Chemistry
Emily M Pieczarka, Duncan S Russell, Kelly S Santangelo, Famke Aeffner, Mary Jo Burkhard
An 11-year-old male castrated mixed-breed dog was presented for exercise intolerance, tetraparesis, and persistent hypoglycemia. Abdominal ultrasound examination revealed 2 nodules within the right limb of the pancreas. Cytology from one nodule was consistent with a carcinoma of neuroendocrine origin, with a primary differential diagnosis of insulinoma. Histologic evaluation and immunohistochemistry for synaptophysin and insulin confirmed the diagnosis of insulinoma. Additionally, there was a solitary nodule of mineralized compact bone composing approximately 60% of the mass...
March 2014: Veterinary Clinical Pathology
Viorica Ionut, Ana Valeria B Castro, Orison O Woolcott, Darko Stefanovski, Malini S Iyer, Josiane L Broussard, Hasmik Mkrtchyan, Miguel Burch, Ram Elazary, Erlinda Kirkman, Richard N Bergman
A major issue of in the treatment of diabetes is the risk of hypoglycemia. Hypoglycemia is detected both centrally and peripherally in the porto-hepatic area. The portal locus for hypoglycemic detection was originally described using the "local irrigation of the liver" approach in a canine model. Further work using portal vein denervation (DEN) in a rodent model characterized portal hypoglycemic sensing in detail. However, recent controversy about the relevance of rodent findings to large animals and humans prompted us to investigate the effect of portal DEN on the hypoglycemic response in the canine, a species with multiple similarities to human glucose homeostasis...
April 2014: Endocrinology
M Isidoro-Ayza, A Lloret, M Bardagí, L Ferrer, J Martínez
A 10-year-old dog presented with convulsive crisis and symmetrical hyperkeratotic cutaneous lesions affecting the abdomen, inguinal area, eyelids, muzzles, both pinnae, and all the paw pads. Hypoglycemia and hyperinsulinemia were the main biochemical findings. A mass 2 cm in diameter was detected within the left pancreatic lobe by ultrasonography. It was surgically removed and histologically and immunohistochemically diagnosed as an insulin-producing pancreatic islet cell carcinoma. The animal was eventually euthanized due to lack of clinical improvement...
July 2014: Veterinary Pathology
Michael E Peterson
Xylitol is a prevalent sugar substitute found in a wide variety of foods, particularly those labeled as "low carb." It is found in many medicines and dental products both for its antibacterial activity and to increase palatability. Originally, this toxin was recognized as a problem in dogs following sugarless gum ingestions. Xylitol is generally nontoxic to mammals except for dogs. In the dog, xylitol induces marked increases in insulin production and occasionally hepatopathy. The clinical syndrome is manifested with signs consistent with profound hypoglycemia, hypokalemia, hypophosphatemia, and acute hepatic failure...
February 2013: Topics in Companion Animal Medicine
Elizabeth Drake Brooks, Dianne Little, Ramamani Arumugam, Baodong Sun, Sarah Curtis, Amanda Demaster, Michael Maranzano, Mark W Jackson, Priya Kishnani, Michael S Freemark, Dwight D Koeberl
Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH...
June 2013: Molecular Genetics and Metabolism
Kazuhiro Hanazaki, Tomoaki Yatabe, Masaki Kobayashi, Yuuki Tsukamoto, Yoshihiko Kinoshita, Masaya Munekage, Hiroyuki Kitagawa
I dedicate this paper to the late Prof. Yukihiko Nosé with all my heart. In 2001, under the direction of Prof. Nosé and Prof. Brunicardi at Baylor College of Medicine, we published a review article entitled "Artificial endocrine pancreas" in JACS. Subsequently, we reported that perioperative tight glycemic control (TGC) using an artificial pancreas (AP) with a closed-loop system could stably maintain near-normoglycemia in total-pancreatectomized dogs. Based on this experimental study in Houston, since 2006, we have introduced perioperative TGC using an AP into clinical use in Kochi...
2013: Bio-medical Materials and Engineering
David Callejas, Christopher J Mann, Eduard Ayuso, Ricardo Lage, Iris Grifoll, Carles Roca, Anna Andaluz, Rafael Ruiz-de Gopegui, Joel Montané, Sergio Muñoz, Tura Ferre, Virginia Haurigot, Shangzhen Zhou, Jesús Ruberte, Federico Mingozzi, Katherine A High, Felix Garcia, Fatima Bosch
Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a "glucose sensor" in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose uptake and correcting hyperglycemia in diabetic mice. Here, we demonstrate long-term efficacy of this approach in a large animal model of diabetes...
May 2013: Diabetes
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