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Glucagon AND Review

Megan E Capozzi, Richard D DiMarchi, Matthias H Tschöp, Brian Finan, Jonathan E Campbell
Glucagon-like peptide-1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of GLP-1R-directed strategies is sub-maximal, and the only potent, sustainable treatment for metabolic dysfunction is bariatric surgery, necessitating the development of novel therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors...
June 13, 2018: Endocrine Reviews
Stephen J Marx
Introduction: Multiple endocrine neoplasia type 1 (MEN1) is complex with regard to clinical expressions, management, and molecular pathways. Advances are being made broadly and in focused aspects. Selected topics are presented for their developments since publication of the most recent MEN1 consensus guidelines 6 years ago. Methods: Topics were selected for clinical impact or broad interest or both. For each topic, information was obtained from original reports and reviews...
April 1, 2018: Journal of Clinical Endocrinology and Metabolism
Majed S Al Yami, Osamah M Alfayez, Razan Alsheikh
The aim of this mixed treatment comparison (MTC) meta-analysis was to determine glucagon like peptide-1 (GLP-1) receptor agonists' effects on cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM). METHODS: A comprehensive, systematic review was conducted using EMBASE and Medline databases. All included trials were large CV outcome trials of GLP-1 agonists versus placebo in T2DM. The primary outcomes of this MTC meta-analysis were death from CV causes, non-fatal MI, and non-fatal stroke...
March 29, 2018: Heart, Lung & Circulation
Dorrin Zarrin Khat, Mansoor Husain
PURPOSE OF REVIEW: In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits...
June 9, 2018: Current Diabetes Reports
Natasha Dave, Jiao Wu, Sandhya Thomas
PURPOSE OF REVIEW: Insulin resistance is an early complication of chronic kidney disease (CKD) associated with worsening cardiovascular outcomes. This review will evaluate mechanisms responsible for CKD-induced insulin resistance and therapies currently available. RECENT FINDINGS: Recent mechanisms have been identified including SIRPα and specific E3 ubiquitin ligases causing insulin resistance in CKD. The hallmark finding in these mechanisms is degradation of the insulin receptor substrate 1 (IRS1) which impairs intracellular insulin signaling and ultimately metabolism...
June 8, 2018: Current Diabetes Reports
Weijia Xie, Xiaoxiao Song, Zhenjie Liu
Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications...
June 4, 2018: Vascular Pharmacology
Steven E Thiessen, Jan Gunst, Greet Van den Berghe
PURPOSE OF REVIEW: Glucagon is known as a key hormone in the control of glucose and amino acid metabolism. Critical illness is hallmarked by a profound alteration in glucose and amino acid metabolism, accompanied by muscle wasting and hypoaminoacidemia. Here we review novel insights in glucagon (patho)physiology and discuss the recently discovered role of glucagon in controlling amino acid metabolism during critical illness. RECENT FINDINGS: The role of glucagon in glucose metabolism is much more complex than originally anticipated, and glucagon has shown to be a key player in amino acid metabolism...
June 4, 2018: Current Opinion in Critical Care
Xiao-Dong Zhuang, Xin He, Da-Ya Yang, Yue Guo, Jian-Gui He, Hai-Peng Xiao, Xin-Xue Liao
BACKGROUND: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included...
June 5, 2018: Cardiovascular Diabetology
John K Smith
This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin...
2018: Frontiers in Physiology
Michael Doumas, Κonstantinos Imprialos, Konstantinos Stavropoulos, Andromachi Reklou, Alexandros Sachinidis, Vasilios G Athyros
BACKGROUND: The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. METHODS: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA)...
June 3, 2018: Current Pharmaceutical Design
Austin Y Lin, Brittny N Tillman, Aaron L Thatcher, Casey R Graves, Mark E Prince
Objectives (1) Compare efficacy of primary medical therapy vs primary surgical intervention in patients with esophageal foreign bodies (EFBs). (2) Investigate variables that may predict successful outcomes in patients treated for EFBs. Study Design Case series with chart review. Setting Single-institution academic tertiary care medical center. Subjects and Methods Adult patients (older than 18 years) seen at the University of Michigan Emergency Department (ED) over an 8-year period with the diagnosis of EFBs (January 1, 2003, to December 31, 2011; N = 250)...
May 1, 2018: Otolaryngology—Head and Neck Surgery
Cheri Hotu, Marc Rémond, Graeme Maguire, Elif Ekinci, Neale Cohen
OBJECTIVE: To determine the impact of an integrated diabetes service involving specialist outreach and primary health care teams on risk factors for micro- and macrovascular diabetes complications in three remote Indigenous Australian communities over a 12-month period. DESIGN: Quantitative, retrospective evaluation. SETTING: Primary health care clinics in remote Indigenous communities in Australia. PARTICIPANTS: One-hundred-and-twenty-four adults (including 123 Indigenous Australians; 76...
June 4, 2018: Australian Journal of Rural Health
Jason D Struthers, Nick Robl, Valerie M Wong, Matti Kiupel
Gastrinoma, an infrequent diagnosis in middle-aged dogs, occurs with nonspecific gastrointestinal morbidity. Laboratory tests can yield a presumptive diagnosis, but definitive diagnosis depends on histopathology and immunohistochemistry. We describe a malignant pancreatic gastrinoma with lymph node metastases and corresponding Zollinger-Ellison syndrome in a Mexican gray wolf ( Canis lupus baileyi) and review this endocrine neoplasm in domestic dogs. A 12-y-old, captive, male Mexican gray wolf developed inappetence and weight loss...
June 1, 2018: Journal of Veterinary Diagnostic Investigation
Panagiotis Anagnostis, Pavlos Siolos, Konstantinos Christou, Nifon K Gkekas, Nikoletta Kosmidou, Vasilios G Athyros, Asterios Karagiannis
Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results...
March 2018: Hormones: International Journal of Endocrinology and Metabolism
Guojun Chen, Jicheng Yu, Zhen Gu
Antidiabetic therapeutics, including insulin as well as glucagon-like peptide 1 (GLP-1) and its analogs, are essential for people with diabetes to regulate their blood glucose levels. Nevertheless, conventional treatments based on hypodermic administration is commonly associated with poor blood glucose control, a lack of patient compliance, and a high risk of hypoglycemia. Closed-loop drug delivery strategies, also known as self-regulated administration, which can intelligently govern the drug release kinetics in response to the fluctuation in blood glucose levels, show tremendous promise in diabetes therapy...
May 1, 2018: Journal of Diabetes Science and Technology
Bharati Kochar, Hans H Herfarth
Teduglutide is an analog of glucagon-like peptide 2 (GLP-2) which is approved for the treatment of patients with short bowel syndrome (SBS) who are dependent on parenteral support. Areas covered: Short bowel syndrome is a rare condition that can result from extensive resection of small bowel, congenital abnormalities, or inflammatory conditions that leads to poor nutrient processing capacity of the intestine. In this review, the safety reported in controlled clinical trials and real-world experience with teduglutide are presented in depth...
June 8, 2018: Expert Opinion on Drug Safety
María Isabel Del Olmo-Garcia, Juan Francisco Merino-Torres
Diabetes mellitus is a chronic disease prevalence of which is high and continually growing. Cardiovascular disease continues to be the leading cause of death in patients with T2DM. The prevention of cardiovascular complications and the cardiovascular safety of treatments should be a primary objective when selecting treatment. Among all the drugs available, the compounds known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) appear to be not just innocuous in terms of CVD but indeed to be beneficial...
2018: Journal of Diabetes Research
Stormi E Gale, Jeannie L Poon, Kristin Watson
Patients with type 2 diabetes mellitus (DM) are known to be at an increased risk for macrovascular complications, and cardiovascular disease (CVD) is one of the greatest drivers of morbidity and mortality in this patient population. Over the past decade, the number of treatment options for type 2 DM has increased. In 2008, the United States Food and Drug Administration mandated an evaluation of cardiovascular (CV) outcomes associated with antihyperglycemic agents. Since that time, the CV risk-benefit profile of many antihyperglycemic treatment modalities have been evaluated; however, results have remained inconsistent...
May 25, 2018: Pharmacotherapy
A J López-Gambero, F Martínez, K Salazar, M Cifuentes, F Nualart
The metabolic and energy state of the organism depends largely on the availability of substrates, such as glucose for ATP production, necessary for maintaining physiological functions. Deregulation in glucose levels leads to the appearance of pathological signs that result in failures in the cardiovascular system and various diseases, such as diabetes, obesity, nephropathy, and neuropathy. Particularly, the brain relies on glucose as fuel for the normal development of neuronal activity. Regions adjacent to the cerebral ventricles, such as the hypothalamus and brainstem, exercise central control in energy homeostasis...
May 24, 2018: Molecular Neurobiology
Luis Rodrigo Cataldo Bascuñan, Claire Lyons, Hedvig Bennet, Isabella Artner, Malin Fex
The exact physiological role for the monoamine serotonin (5-HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signaling network in islets involving 5-HT is being unraveled. With more than fourteen different 5-HT receptors expressed in human islets, and receptor independent mechanisms in insulin producing β-cells, our understanding of 5-HT's regulation of insulin secretion is increasing...
May 23, 2018: Acta Physiologica
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