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Z Li, FA Karlsson, and S Sandler

The aim of this study was to investigate the alpha cell population during the development of type 1 diabetes following multiple low-dose streptozotocin administration in mice. For this purpose C57BL/Ks male mice were injected with streptozotocin (40 mg/kg body weight for 5 days). Development of hyperglycemia was monitored over 28 days and a morphometric analysis of islet endocrine cells was performed. A reduction of islet cell area was observed after two injections of streptozotocin. The subsequent decrease of the area throughout the study period averaged 35%. Insulin-positive beta cells gradually disappeared from the identified islets. Hyperglycemia was present from day 7 onwards and in parallel with hyperglycemia, insulitis developed. An analysis of the alpha cell number per islet area revealed a 2- to 3-fold increase in this cell population, with the highest value on day 21. Confocal microscopy analysis of the ICA 512 protein tyrosine phosphatase revealed strong expression in the alpha cells at day 21, suggesting high secretory activity in the diabetic state. It is concluded that multiple low-dose streptozotocin treatment of C57BL/Ks male mice causes the disappearance of a fraction of the islets of Langerhans. In the remaining islet tissue an expansion of alpha cells occurs, reflecting a loss of intraislet beta cells as well as a regeneration of alpha cells.

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Yoswaris Semaming, Sirinart Kumfu, Patchareewan Pannangpetch, Siriporn C Chattipakorn, and Nipon Chattipakorn

Oxidative stress has been shown to play an important role in the pathogenesis of diabetes-induced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague–Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50  mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM.

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Louise J N Jensen, Larry Denner, Bieke F Schrijvers, Ronald G Tilton, Ruth Rasch, and Allan Flyvbjerg

Introduction Diabetic nephropathy develops in 15–25% of all patients with type 1 diabetes and is one of the leading causes of end-stage renal failure. Accordingly, development of diabetic nephropathy is associated with a considerable

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Ronald Gonzalez, Benjamin K Reingold, Xiaodong Gao, Mandeep P Gaidhu, Robert G Tsushima, and Suraj Unniappan

expression and nesfatin-1-ir in the pancreas of mice with type 1 diabetes, while a significant increase was observed in the pancreas of diet-induced obese (DIO) mice with type 2 diabetes. Our new findings indicate that nesfatin-1 is a novel glucose

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Richard W Nelson and Claudia E Reusch

various forms of the disease in dogs and cats. Diabetes in dogs resembles type 1 diabetes in humans while diabetes in most cats resembles type 2 diabetes. This article focuses on our current understanding of the etiology of diabetes in dogs vs cats and

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Christopher J Burns, Shanta J Persaud, and Peter M Jones

Langerhans into individuals with Type 1 diabetes has largely removed this insulin dependency ( Shapiro et al. 2000 , Ryan et al. 2001 ). However, the application of this treatment is restricted by the very limited availability of primary human islets

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Anna Milanesi, Jang-Won Lee, Qijin Xu, Laura Perin, and John S Yu

may be a promising approach for cell replacement in type 1 diabetes. However, islet availability for allogeneic transplantation is limited ( Lakey et al . 2006 , Shapiro et al . 2006 ). In addition, understanding the origin of new β-cells in adults

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Sharon H Chou and Christos Mantzoros

Improves bone mineral density  Type 1 diabetes Hypogonadotropic hypogonadism, infertility with uncontrolled disease In mice models  Restores Kiss1 gene expression, normalizes LH and sex steroids  Improves glucose control and variability

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Lucy M Hinder, Anuradha Vivekanandan-Giri, Lisa L McLean, Subramaniam Pennathur, and Eva L Feldman

Introduction According to statistics published by the Centers for Disease Control (2011) , ∼8% of the US population has diabetes mellitus, with 1.9 million new cases diagnosed in 2010. Although both type 1 diabetes and type 2 diabetes are

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Corinne A Schuyler, Nga N Ta, Yanchun Li, Maria F Lopes-Virella, and Yan Huang

conducted on 1441 patients with type 1 diabetes ( Nathan et al . 2005 ). After giving patients either conventional or intensive insulin treatment, which lowered HbAlc level to 9.1 or 7.4% respectively, for 6.5 years and following up patients for 17 years