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https://www.readbyqxmd.com/read/27911591/type-b-insulin-resistance-masquerading-as-ovarian-hyperthecosis
#1
Rebecca J Brown, Jalaja Joseph, Elaine Cochran, Cornelia Gewert, Robert Semple, Phillip Gorden
CONTEXT: Hyperinsulinemia can lead to pathologic ovarian growth and androgen production. CASE DESCRIPTION: A 29 year old woman developed an autoantibody to the insulin receptor (Type B insulin resistance), causing extreme insulin resistance and hyperinsulinemia. Testosterone levels were elevated to the adult male range. Treatment with gonadotropin releasing hormone (GnRH) analog led to normalization of testosterone, despite persistent extreme insulin resistance...
December 2, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27909794/prescription-of-oral-antidiabetic-drugs-in-tyrol-data-from-the-tyrol-diabetes-registry-2012-2015
#2
Lukas Lunger, Andreas Melmer, Willi Oberaigner, Marco Leo, Martin Juchum, Karin Pölzl, Johannes Gänzer, Martha Innerebner, Egon Eisendle, Gertrud Beck, Hermann Kathrein, Bernhard Heindl, Hans Robert Schönherr, Monika Lechleitner, Herbert Tilg, Christoph Ebenbichler
Diabetes mellitus affects 9% of the adult population worldwide and the economic burden of the disease is growing exponentially. In type 2 diabetes mellitus (T2DM), when life style interventions fail to achieve treatment targets, oral antidiabetic drugs are prescribed to improve glycemic control. Several new oral antidiabetics have been launched in the last few years, which enlarged the spectrum of available treatment options in T2DM. The present study aimed to examine T2DM treatment patterns in a cohort of 7769 patients recruited from the Diabetes Registry Tyrol (DRT) with at least one visit from 2012-2015...
December 1, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27903228/synthesis-and-evaluation-of-the-hypoglycemic-and-hypolipidemic-activity-of-novel-sulfonamide-benzothiazole-derivatives-of-benzylidene-2-4-thiazolidnedione
#3
Abbas Ahmadi, Mohsen Khalili, Lida Sohrabi, Nazanin Delzendeh, Babak Nahri-Niknafs, Fariba Ansari
Thiazolidinediones (TZDs) and sulfonamides are important and highly consumption class of antidiabetic drugs having insulin sensitizing and stimulating properties in patients with type 2 diabetes, respectively. In this paper, some novel benzothiazole derivatives of TZD-sulfonamides were synthesized (I-IV) and evaluated for anti-hyperglycemic and anti-hyperlipidemic activities in the STZ-induced diabetic rat model. Results indicated that all new conjugated drugs showed significant hypoglycemic activities compared to the control animals that were better for I and IV than others...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27896318/insulin-elevates-leptin-secretion-and-mrna-levels-via-cyclic-amp-in-3t3-l1-adipocytes-deprived-of-glucose
#4
Tomomi Tsubai, Yukihiro Noda, Kazuma Ito, Makoto Nakao, Yusuke Seino, Yutaka Oiso, Yoji Hamada
AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin signal transduction in adipocytes cultured under glucose-free or normal conditions. METHODS: Differentiated 3T3-L1 adipocytes were stimulated with insulin in combination with inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free or normal conditions...
November 2016: Heliyon
https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#5
S ThanThan, Y Asada, T Saito, K Ochiiwa, H Zhao, S W Naing, H Kuwayama
The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly(2), Glu(3)]-OXM), a glucagon analog ([Gly(2), Glu(3)]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly(2), Glu(3)]-glucandin) were synthesized by substituting with Gly(2), Glu(3) at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments...
November 2, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/27884723/ir-and-igf-1r-expression-affects-insulin-induced-proliferation-and-dna-damage
#6
Eman Maher Othman, Tahanee Altabaa, Henning Hintzsche, Helga Stopper
Diabetes mellitus type 2 is in its prediagnostic and early phase characterized by hyperinsulinemia. Previously, we pointed out hyperinsulinemia as a potential link between diabetes mellitus and the increased cancer risk that is associated with this disease through its induction of oxidative stress and DNA damage. In the present study, we address the relationship between the induction of proliferation and genomic damage in vitro in cell lines with different expression of the insulin and the IGF-1 receptors after treating the cells with insulin and the insulin analog glargine...
November 21, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27879355/pregnancy-outcomes-in-women-with-diabetes-lessons-learned-from-clinical-research-the-2015-norbert-freinkel-award-lecture
#7
Elisabeth R Mathiesen
Among women with diabetes, the worst pregnancy outcome is seen in the subgroup of women with diabetic nephropathy. Development of severe preeclampsia that leads to early preterm delivery is frequent. Predictors and pathophysiological mechanisms for the development of preeclampsia among women with diabetes and observational studies that support antihypertension treatment for pregnant women with microalbuminuria or diabetic nephropathy preventing preeclampsia and early preterm delivery are presented here. Obtaining and maintaining strict glycemic control before and during pregnancy is paramount to prevent preterm delivery...
December 2016: Diabetes Care
https://www.readbyqxmd.com/read/27879196/treatment-persistence-in-the-use-of-basal-insulins-in-poland-and-germany%C3%A2
#8
Wolfgang Rathmann, Marcin Czech, Edward Franek, Karel Kostev
AIMS: To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany. METHODS: Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests)...
November 23, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27875310/extending-halogen-based-medicinal-chemistry-to-proteins-iodo-insulin-as-a-case-study
#9
Krystel El Hage, Vijay Pandyarajan, Nelson B Phillips, Brian J Smith, John G Menting, Jonathan Whittaker, Michael C Lawrence, Markus Meuwly, Michael A Weiss
Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr(B26)) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomic-level simulations of 3-I-Tyr(B26)-insulin to predict its structural features and (ii) tested these predictions by X-ray crystallography...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27857836/refractory-hypoglycemia-in-a-patient-with-functional-adrenal-cortical-carcinoma
#10
Katia Regina Marchetti, Maria Adelaide Albergaria Pereira, Arnaldo Lichtenstein, Edison Ferreira Paiva
: Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27846338/an-evolutionary-perspective-on-basal-insulin-in-diabetes-treatment-innovations-in-insulin-insulin-degludec-u-100-and-u-200
#11
Athena Philis-Tsimikas
Insulin degludec (IDeg) is a long-acting basal human insulin analog produced using recombinant DNA technology. The insulin structure is modified at the B30 position to allow a di-hexamer conformation in the presence of phenol and zinc.
October 2016: Journal of Family Practice
https://www.readbyqxmd.com/read/27846336/an-evolutionary-perspective-on-basal-insulin-in-diabetes-treatment-role-of-insulin-therapy-in-diabetes
#12
Helena W Rodbard
The availability of human insulin and subsequently insulin analogs that more closely mimic the body's physiology have contributed to increased safety in patients with diabetes and a greater role in patients with T2DM. This greater role is supported by clear evidence that early use of insulin in T2DM results in long-term improvements in glycemic control and beta-cell function compared with oral agents.
October 2016: Journal of Family Practice
https://www.readbyqxmd.com/read/27833848/neutral-ceramidase-enriched-exosomes-prevent-palmitic-acid-induced-insulin-resistance-in-h4iiec3-hepatocytes
#13
Qun Zhu, Rongping Zhu, Junfei Jin
Oversupply of free fatty acids such as palmitic acid (PA) from the portal vein may cause liver insulin resistance. Production of reactive oxygen species plays a pivotal role in PA-induced insulin resistance in H4IIEC3 hepatocytes. Recently, we found that exosomes secreted from INS-1 cells that were transfected with neutral ceramidase (NCDase) plasmids had raised NCDase activity; these NCDase-enriched exosomes could inhibit PA-induced INS-1 cell apoptosis. Here, we showed that PA reduced insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 2 and decreased insulin-stimulated uptake of the fluorescent glucose analog 2-NBDG, confirming that insulin resistance occurred in PA-treated H4IIEC3 cells...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27826244/judicious-toggling-of-mtor-activity-to-combat-insulin-resistance-and-cancer-current-evidence-and-perspectives
#14
REVIEW
Pei Shi Ong, Louis Z Wang, Xiaoyun Dai, Sheng Hsuan Tseng, Shang Jun Loo, Gautam Sethi
The mechanistic target of rapamycin (mTOR), via its two distinct multiprotein complexes, mTORC1, and mTORC2, plays a central role in the regulation of cellular growth, metabolism, and migration. A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance. On the other hand, aberrant mTORC1 and mTORC2 signaling via either genetic alterations or increased expression of proteins regulating mTOR and its downstream targets have contributed to cancer development...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27815568/diabetes-drug-effects-on-the-skeleton
#15
Manju Chandran
Diabetes be it type 1 or type 2 is associated with an increased risk of fragility fractures. The mechanisms underlying this increased risk are just being elucidated. Anti-diabetes medications are crucial for maintaining glucose control and for preventing micro- and macrovascular complications in diabetes. However, they may modulate fracture risk in diabetes in different ways. Thiazolidinediones have demonstrated an unfavorable effect on the skeleton, while metformin and sulfonylureas may have a neutral if not beneficial effect on bone...
November 4, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27807910/glargine-co-administration-with-intravenous-insulin-in-pediatric-diabetic-ketoacidosis-is-safe-and-facilitates-transition-to-a-subcutaneous-regimen
#16
V Sanoe Harrison, Stacy Rustico, Andrew A Palladino, Christine Ferrara, Colin Patrick Hawkes
BACKGROUND: Diabetes ketoacidosis (DKA) is a common presentation and complication of type 1 diabetes (T1D). While intravenous insulin is typically used to treat acute metabolic abnormalities, the transition from intravenous to subcutaneous treatment can present a challenge. We hypothesize that co-administration of glargine, a subcutaneous long-acting insulin analog, during insulin infusion may facilitate a flexible and safe transition from intravenous to subcutaneous therapy. OBJECTIVE: To determine if the practice of administering subcutaneous glargine during intravenous insulin is associated with an increased risk of hypoglycemia, hypokalemia, or other complications in children with DKA...
November 3, 2016: Pediatric Diabetes
https://www.readbyqxmd.com/read/27799746/insulin-glargine-300-u-ml-in-the-management-of-diabetes-clinical-utility-and-patient-perspectives
#17
REVIEW
Bastiaan E de Galan
There is ongoing interest in optimizing basal insulin treatment by developing insulins with a flat pharmacological profile, a long duration of action (typically beyond 24 hours) and minimum day-to-day variation. Glargine-300 is a modified form of the long-acting insulin analog glargine in that it has been concentrated at 300 units/mL rather than the conventional 100 units/mL. Glargine-300 has a longer duration of action and a flatter pharmacological profile than original glargine-100. This property allows for more flexibility around the timing of administration, when injected once per day...
2016: Patient Preference and Adherence
https://www.readbyqxmd.com/read/27789139/design-synthesis-and-evaluation-of-2s-4r-ketoconazole-sulfonamide-analogs-as-potential-treatments-for-metabolic-syndrome
#18
Benjamin E Blass, Pravin Iyer, Magid Abou-Gharbia, Wayne E Childers, John C Gordon, Mercy Ramanjulu, George Morton, Premkumar Arumugam, Joshodeep Boruwa, John Ellingboe, Sayan Mitra, Rajashekar Reddy Nimmareddy, Shalini Paliwal, Jamallamudi Rajasekhar, Savithiri Shivakumar, Pratima Srivastava, Raghuram S Tangirala, Konda Venkataramanaiah, Mahesh Yanamandra
Metabolic Syndrome, also referred to as 'Syndrome X' or 'Insulin Resistance Syndrome,' remains a major, unmet medical need despite over 30years of intense effort. Recent research suggests that there may be a causal link between this condition and abnormal glucocorticoid processing. Specifically, dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis leads to increased systemic cortisol concentrations. Cushing' syndrome, a disorder that is also typified by a marked elevation in levels of cortisol, produces clinical symptomology that is similar to those observed in MetS, and they can be alleviated by decreasing circulating cortisol concentrations...
December 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27777568/growth-hormone-releasing-hormone-in-diabetes
#19
Leonid E Fridlyand, Natalia A Tamarina, Andrew V Schally, Louis H Philipson
Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27776453/individualized-patient-centered-use-of-lixisenatide-for-the-treatment-of-type-2-diabetes-mellitus
#20
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
November 3, 2016: Expert Opinion on Drug Metabolism & Toxicology
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