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Hypoglycemia dog insulin

H Fink, C Herbert, C Gilor
Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG ("isoglycemic clamp")...
April 10, 2018: Domestic Animal Endocrinology
Mary Courtney Moore, David E Kelley, Raul C Camacho, Peter Zafian, Tian Ye, Songnian Lin, Niels C Kaarsholm, Ravi Nargund, Terri M Kelly, Margaret Van Heek, Stephen F Previs, Christopher Moyes, Marta S Smith, Ben Farmer, Phil Williams, Alan D Cherrington
We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3-3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2)...
March 14, 2018: Diabetes
Constantin Ionescu-Tirgoviste, Octavian Buda
The purpose of this article is to describe the research of Nicolae Constantin Paulescu and to emphasize his role in the discovery of insulin. METHODS: We made a thorough review of the literature and research in the Romanian Academy Archive in order to find adequate references. RESULTS: In 1912 N.C. Paulescu analysed the clinical and biochemical alterations in diabetic patients and in dogs after performing a pancreatectomy, that apart hyperglycemia and glycosuria (carbohydrate metabolism), had noted also changes in lipid and protein metabolism...
December 2017: Acta Medico-historica Adriatica: AMHA
Ellen Behrend, Amy Holford, Patty Lathan, Renee Rucinsky, Rhonda Schulman
Diabetes mellitus (DM) is a common disease encountered in canine and feline medicine. The 2018 AAHA Diabetes Management Guidelines for Dogs and Cats revise and update earlier guidelines published in 2010. The 2018 guidelines retain much of the information in the earlier guidelines that continues to be applicable in clinical practice, along with new information that represents current expert opinion on controlling DM. An essential aspect of successful DM management is to ensure that the owner of a diabetic dog or cat is capable of administering insulin, recognizing the clinical signs of inadequately managed DM, and monitoring blood glucose levels at home, although this is ideal but not mandatory; all topics that are reviewed in the guidelines...
January 2018: Journal of the American Animal Hospital Association
Niels C Kaarsholm, Songnian Lin, Lin Yan, Theresa Kelly, Margaret van Heek, James Mu, Margaret Wu, Ge Dai, Yan Cui, Yonghua Zhu, Ester Carballo-Jane, Vijay Reddy, Peter Zafian, Pei Huo, Shuai Shi, Valentyn Antochshuk, Aimie Ogawa, Franklin Liu, Sandra C Souza, Wolfgang Seghezzi, Joseph L Duffy, Mark Erion, Ravi P Nargund, David E Kelley
Insulin has a narrow therapeutic index, reflected in a small margin between a dose that achieves good glycemic control and one that causes hypoglycemia. Once injected, the clearance of exogenous insulin is invariant regardless of blood glucose, aggravating the potential to cause hypoglycemia. We sought to create a "smart" insulin, one that can alter insulin clearance and hence insulin action in response to blood glucose, mitigating risk for hypoglycemia. The approach added saccharide units to insulin to create insulin analogs with affinity for both the insulin receptor (IR) and mannose receptor C-type 1 (MR), which functions to clear endogenous mannosylated proteins, a principle used to endow insulin analogs with glucose responsivity...
February 2018: Diabetes
Janet Kovak Mcclaran, Philippa Pavia, Anthony J Fischetti, Taryn A Donovan
Laparoscopic partial pancreatectomy has been performed in experimental canine studies and has been evaluated in human medicine but has not been reported in a clinical veterinary case. The authors present a 9 yr old field spaniel with weakness and hypoglycemia with insulin levels and Amended Insulin: Glucose Ratio results equivocal for a pancreatic insulinoma. Multiple abdominal ultrasounds did not detect the tumor, yet dual-phase computed tomographic angiography revealed the presence of a focal hypoattenuating nodule in the left lobe of the pancreas...
September 11, 2017: Journal of the American Animal Hospital Association
Amanda P Siegel, Ali Daneshkhah, Dana S Hardin, Sudhir Shrestha, Kody Varahramyan, Mangilal Agarwal
Diabetes is a disease that involves dysregulation of metabolic processes. Patients with type 1 diabetes (T1D) require insulin injections and measured food intake to maintain clinical stability, manually tracking their results by measuring blood glucose levels. Low blood glucose levels, hypoglycemia, can be extremely dangerous and can result in seizures, coma, or even death. Canines trained as diabetes alert dogs (DADs) have demonstrated the ability to detect hypoglycemia from breath, which led us to hypothesize that hypoglycemia, a metabolic dysregulation leading to low blood glucose levels, could be identified through analyzing volatile organic compounds (VOCs) contained within breath...
June 1, 2017: Journal of Breath Research
Justin M Gregory, Noelia Rivera, Guillaume Kraft, Jason J Winnick, Ben Farmer, Eric J Allen, E Patrick Donahue, Marta S Smith, Dale S Edgerton, Phillip E Williams, Alan D Cherrington
The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained ( group 1 ) or hypoglycemia (≈45 mg/dl) was allowed to occur. There were three hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input ( group 2 ), one in which autoregulation occurred in the presence of norepinephrine (NE) signaling to fat and muscle ( group 3 ), and one in which autoregulation occurred in the presence of NE signaling to fat, muscle, and liver ( group 4 )...
September 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
Christof Westenfelder, Anna Gooch, Zhuma Hu, Jon Ahlstrom, Ping Zhang
Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end-organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life-long need for often-toxic antirejection drugs. Coadministering islets with bone marrow-derived mesenchymal stem cells (MSCs) that exert robust immune-modulating, anti-inflammatory, anti-apoptotic, and angiogenic actions, improves intrahepatic islet survival and function...
July 2017: Stem Cells Translational Medicine
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
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