scholarly journals Long-term treatment with the ghrelin receptor antagonist [d-Lys3]-GHRP-6 does not improve glucose homeostasis in nonobese diabetic MKR mice

2018 ◽  
Vol 314 (1) ◽  
pp. R71-R83 ◽  
Author(s):  
Rasha Mosa ◽  
Lili Huang ◽  
Hongzhuo Li ◽  
Michael Grist ◽  
Derek LeRoith ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Glucose Homeostasis ◽  
Term Treatment ◽  
Ghrelin Receptor ◽  
Nonobese Diabetic ◽  
Long Term Treatment ◽  
Ghrelin Receptor Antagonist

Long-term treatment with the ghrelin receptor antagonist [d-Lys3]-GHRP-6 does not improve glucose homeostasis in nonobese diabetic MKR mice. Am J Physiol Regul Integr Comp Physiol 314: R71–R83, 2018. First published September 13, 2017; doi: 10.1152/ajpregu.00157.2017 .—Ghrelin secretion has been associated with increased caloric intake and adiposity. The expressions of ghrelin and its receptor (GHS-R1a) in the pancreas has raised the interest about the role of ghrelin in glucose homeostasis. Most of the studies showed that ghrelin promoted hyperglycemia and inhibited insulin secretion. This raised the interest in using GHS-R1a antagonists as therapeutic targets for type 2 diabetes. Available data of GHS-R antagonists are on a short-term basis. Moreover, the complexity of GHS-R1a signaling makes it difficult to understand the mechanism of action of GHS-R1a antagonists. This study examined the possible effects of long-term treatment with a GHS-R1a antagonist, [d-Lys3]-growth hormone-releasing peptide (GHRP)-6, on glucose homeostasis, food intake, and indirect calorimetric parameters in nonobese diabetic MKR mice. Our results showed that [d-Lys3]-GHRP-6 (200 nmol/mouse) reduced pulsatile growth hormone secretion and body fat mass as expected but worsened glucose and insulin intolerances and increased cumulative food intake unexpectedly. In addition, a significant increase in blood glucose and decreases in plasma insulin and C-peptide levels were observed in MKR mice following long-term [d-Lys3]-GHRP-6 treatment, suggesting a direct inhibition of insulin secretion. Immunofluorescence staining of pancreatic islets showed a proportional increase in somatostatin-positive cells and a decrease in insulin-positive cells in [d-Lys3]-GHRP-6-treated mice. Furthermore, [d-Lys3]-GHRP-6 stimulated food intake on long-term treatment via reduction of proopiomelanocortin gene expression and antagonized GH secretion via reduced growth hormone-releasing hormone gene expression in hypothalamus. These results demonstrate that [d-Lys3]-GHRP-6 is not completely opposite to ghrelin and may not be a treatment option for type 2 diabetes.

scholarly journals Hypomagnesemia Induced by Long-Term Treatment with Proton-Pump Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Simone Janett ◽  
Pietro Camozzi ◽  
Gabriëlla G. A. M. Peeters ◽  
Sebastiano A. G. Lava ◽  
Giacomo D. Simonetti ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Term Treatment ◽  
Cross Sectional ◽  
Magnesium Metabolism ◽  
Poor Renal Function ◽  
Long Term Treatment

In 2006, hypomagnesemia was first described as a complication of proton-pump inhibitors. To address this issue, we systematically reviewed the literature. Hypomagnesemia, mostly associated with hypocalcemic hypoparathyroidism and hypokalemia, was reported in 64 individuals on long-term proton-pump inhibitors. Hypomagnesemia recurred following replacement of one proton-pump inhibitor with another but not with a histamine type-2 receptor antagonist. The association between proton-pump inhibitors and magnesium metabolism was addressed in 14 case-control, cross-sectional studies. An association was found in 11 of them: 6 reports found that the use of proton-pump inhibitors is associated per se with a tendency towards hypomagnesemia, 2 found that this tendency is more pronounced in patients concurrently treated with diuretics, carboplatin, or cisplatin, and 2 found a relevant tendency to hypomagnesemia in patients with poor renal function. Finally, findings likely reflecting decreased intestinal magnesium uptake were observed on treatment with proton-pump inhibitors. Three studies did not disclose any relationship between magnesium metabolism and treatment with histamine type-2 receptor antagonists. In conclusion, proton-pump inhibitors may cause hypomagnesemia. In these cases, switching to a histamine type-2 receptor antagonist is advised.

Effects of Long-term Treatment of Linagliptin on Glycemic Control in Japanese Patients with Type 2 Diabetes

2018 ◽  
Vol 14 (8) ◽  
pp. 1153-1159
Author(s):  
Masataka Kusunoki ◽  
Yukie Natsume ◽  
Hideyo Tsutsui ◽  
Tetsuro Miyata ◽  
Kazuhiko Tsutsumi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Japanese Patients ◽  
Term Treatment ◽  
Long Term Treatment

Hormonal changes in gilts receiving bromocriptine orally during gestation

2000 ◽  
Vol 80 (2) ◽  
pp. 373-376 ◽  
Author(s):  
S. Horth ◽  
C. Farmer
Keyword(s):  
Growth Hormone ◽  
Key Words ◽  
Initial Treatment ◽  
Term Treatment ◽  
Hormonal Changes ◽  
Long Term Treatment ◽  
Blood Profiles

Pregnant gilts received a placebo (CTL; n = 7) or 10 mg of bromocriptine orally (Bromo; n = 7) thrice daily from days 70 to 107 of gestation. Blood profiles of prolactin (PRL), growth hormone (GH) and cortisol were obtained on day 70, after the first treatment with bromocriptine, and on day 107 of gestation. On day 70, concentrations of PRL, GH and cortisol were not affected (P > 0.1) by bromocriptine. By day 107, bromocriptine decreased concentrations of PRL (P < 0.01) whereas concentrations of GH and cortisol were not affected (P > 0.1). Results indicate that long-term treatment with bromocriptine inhibits PRL secretion without affecting GH and cortisol concentrations, while no changes are present within 8 h of initial treatment. Key words: Gilt, gestation, bromocriptine, prolactin

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