scholarly journals Permanent Deiodinase Type 2 Deficiency Strongly Perturbs Zebrafish Development, Growth, and Fertility

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3668-3681 ◽  
Author(s):  
Anne M. Houbrechts ◽  
Julie Delarue ◽  
Isabelle J. Gabriëls ◽  
Jo Sourbron ◽  
Veerle M. Darras
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Zinc Finger Nucleases ◽  
Long Term Effects ◽  
Compensatory Mechanisms ◽  
Iodothyronine Deiodinases ◽  
Swim Bladder Inflation ◽  
Conserved Amino Acids

Iodothyronine deiodinases are selenocysteine-containing enzymes that activate or inactivate thyroid hormones (THs). Deiodinase type 2 (Dio2) catalyzes the conversion of the prohormone T4 into the transcriptionally active T3 and is the predominant activating deiodinase in zebrafish. Using zinc finger nucleases, we generated two different dio2−/− mutant zebrafish lines to investigate the physiological function of this TH activator. The first line contains a deletion of 9 bp, resulting in an in-frame elimination of three conserved amino acids. The other line is characterized by an insertion of 4 bp, leading to the introduction of a premature stop-codon. Both lines completely lack Dio2 activity, resulting in a strong reduction of T3 abundancy in all tissues tested. Early development is clearly perturbed in these animals, as shown by a diverse set of morphometric parameters, defects in swim bladder inflation, and disturbed locomotor activity tested between 1 and 7 days after fertilization. Permanent Dio2 deficiency also provokes long-term effects because growth and especially fertility are severely hampered. Possible compensatory mechanisms were investigated in adult dio2−/− mutants, revealing a down-regulation of the inactivating deiodinase Dio3 and TH receptor transcript levels. As the first nonmammalian model with permanent Dio2 deficiency, these mutant zebrafish lines provide evidence that Dio2 is essential to assure normal development and to obtain a normal adult phenotype.

Long-Term Effects of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Surgery on Type 2 Diabetes Mellitus in Morbidly Obese Subjects

2012 ◽  
Vol 256 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Amanda Jiménez ◽  
Roser Casamitjana ◽  
Lílliam Flores ◽  
Judith Viaplana ◽  
Ricard Corcelles ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Morbidly Obese ◽  
Long Term Effects ◽  
Obese Subjects

Treatments for Pathological Gambling and Other Impulse Control Disorders

2007 ◽  
pp. 561-578 ◽  
Author(s):  
Jon E. Grant ◽  
Marc N. Potenza
Keyword(s):  
Pathological Gambling ◽  
Pharmacological Treatment ◽  
Impulse Control ◽  
Behavioral Therapy ◽  
Impulse Control Disorders ◽  
Long Term Effects ◽  
Drug Treatments

Several controlled outcome studies (Type 1 and Type 2) suggest that specific behavioral (e.g., cognitive-behavioral therapy [CBT]) and pharmacological (e.g., naltrexone, nalmefene, lithium) treatments significantly reduce the symptoms of pathological gambling in the short term compared with wait-list or placebo. Although long-term effects of manual-based CBT have been observed in several small studies, the long-term benefits of pharmacological treatment have not been adequately tested. No studies combining behavioral and pharmacological therapies have been published to date. Thus, the potential benefit of combining behavioral and drug treatments for pathological gambling remains to be investigated systematically. Although several studies (Type 1 and Type 2) suggest that CBT is effective for trichotillomania, pharmacological treatment studies for this disorder have shown mixed results. Similarly, controlled pharmacological studies (Type 1 and Type 2) of compulsive buying have demonstrated mixed results. Limited treatment studies exist for other impulse control disorders (kleptomania, intermittent explosive disorder), although various pharmacological and psychological treatments have shown promise in uncontrolled studies.

Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients

2020 ◽  
Vol 98 (6) ◽  
pp. 400-411 ◽  
Author(s):  
Hacene Bouras ◽  
Sara R. Roig ◽  
Steef Kurstjens ◽  
Cees J.J. Tack ◽  
Mohamed Kebieche ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Surface ◽  
Fine Tuning ◽  
Metformin Treatment ◽  
Long Term Effects ◽  
Short Term ◽  
Metformin Therapy ◽  
Diabetes Patients

Metformin therapy is associated with lower serum magnesium (Mg2+) levels in type 2 diabetes patients. The TRPM6 channel determines the fine-tuning of Mg2+ (re)absorption in intestine and kidney. Therefore, we aimed to investigate the short- and long-term effects of metformin on TRPM6. Patch clamp recordings and biotinylation assays were performed upon 1 h of incubation with metformin in TRPM6-transfected HEK293 cells. Additionally, 24 h of treatment of mDCT15 kidney and hCaco-2 colon cells with metformin was applied to measure the effects on endogenous TRPM6 expression by quantitative real-time PCR. To assess Mg2+ absorption, 25Mg2+ uptake measurements were performed using inductively coupled plasma mass spectrometry. Short-term effects of metformin significantly increased TRPM6 activity and its cell surface trafficking. In contrast, long-term effects significantly decreased TRPM6 mRNA expression and 25Mg2+ uptake. Metformin lowered TRPM6 mRNA levels independently of insulin- and AMPK-mediated pathways. Moreover, in type 2 diabetes patients, metformin therapy was associated with lower plasma Mg2+ concentrations and fractional excretion of Mg2+. Thereby, short-term metformin treatment increases TRPM6 activity explained by enhanced cell surface expression. Conversely, long-term metformin treatment results in downregulation of TRPM6 gene expression in intestine and kidney cells. This long-term effect translated in an inverse correlation between metformin and plasma Mg2+ concentration in type 2 diabetes patients.

scholarly journals Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis

2016 ◽  
Vol 89 (6) ◽  
pp. 1380-1387 ◽  
Author(s):  
Vera Krane ◽  
Kay-Renke Schmidt ◽  
Lena J. Gutjahr-Lengsfeld ◽  
Johannes F.E. Mann ◽  
Winfried März ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Long Term Effects

scholarly journals Overweight and diabetes prevention: is a low-carbohydrate–high-fat diet recommendable?

2018 ◽  
Vol 57 (4) ◽  
pp. 1301-1312 ◽  
Author(s):  
Fred Brouns
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Carbohydrate Content ◽  
Food Sources ◽  
Long Term Effects ◽  
High Fat ◽  
Functional Changes ◽  
Low Carbohydrate

Abstract In the past, different types of diet with a generally low-carbohydrate content (< 50–< 20 g/day) have been promoted, for weight loss and diabetes, and the effectiveness of a very low dietary carbohydrate content has always been a matter of debate. A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of fat and to a lesser extent, also protein. Accordingly, using the term “low carb–high fat” (LCHF) diet is most appropriate. Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to be difficult. A non-ketogenic diet supplying 100–150 g carbohydrate/day, under good control, may be more practical. (4) There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.

scholarly journals Cardiovascular Effects of Long-Term Central and Peripheral Administration of Urocortin, Corticotropin-Releasing Factor, and Adrenocorticotropin in Sheep

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5598-5604 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
P. Burns ◽  
D. A. Denton ◽  
B. Purcell ◽  
...  
Keyword(s):  
Stress Response ◽  
Arterial Pressure ◽  
Cardiovascular Effects ◽  
Corticotropin Releasing Factor ◽  
Central Administration ◽  
Long Term Effects ◽  
Cardiovascular Actions ◽  
Term Administration

Abstract The neuroendocrine hormones ACTH and corticotropin- releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important because they may differ considerably from their acute actions, and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN, and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (icv) or iv over 4 d at 5 μg/h. UCN infused icv or iv caused a prolonged increase in heart rate (HR) (P &lt; 0.01) and a small increase in mean arterial pressure (MAP) (P &lt; 0.05). CRF infused icv or iv progressively increased MAP (P &lt; 0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P &lt; 0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with icv and iv infusions of UCN. These responses are probably mediated by CRF type 2 receptors because they were not reproduced by infusions of CRF.

scholarly journals Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus

2009 ◽  
Vol 169 (6) ◽  
pp. 616 ◽  
Author(s):  
Adriaan Kooy ◽  
Jolien de Jager ◽  
Philippe Lehert ◽  
Daniël Bets ◽  
Michiel G. Wulffelé ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Macrovascular Disease ◽  
Long Term Effects
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