Does short-term administration of glucagon-like peptide type 2 affect bone mass and markers of bone remodeling in short bowel patients?

Increased fat mass contributes to bone deterioration. Glucagon-like peptide 1 (GLP-1) and its related peptide exendin 1–39 amide (Ex-4), two lipid-lowering peptides, exert osteogenic effects in diabetic states. We examined the actions of 3-day administration of GLP-1 or Ex-4 on bone remodeling markers and on bone mass and structure in hyperlipidic (HL) and hypercaloric rats. Wistar rats on a hyperlipidemic diet for 35 days were subcutaneously administered GLP-1 (0.86 nmol/kg per h), Ex-4 (0.1 nmol/kg per h), or saline (control) by continuous infusion for 3 days. After killing, tibiae were removed for total RNA and protein isolation, as well as femurs and L1–L4 vertebrae for bone mass and quality assessment. Body weight and plasma insulin were unaltered in HL rats, which showed osteopenia (by dual-energy X-ray absorptiometry), associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. GLP-1 or Ex-4 administration decreased the levels of glucose, triglycerides, and total cholesterol in plasma but increased osteocalcin (OC) gene expression and the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio – at the expense of an augmented OPG – above corresponding control values in the tibia. Each tested peptide similarly reversed the decreased femoral and vertebral bone mass in these rats, whereas the deteriorated trabecular structure in the vertebrae improved associated with normalization of bone remodeling. These findings demonstrate that GLP-1 and Ex-4 are similarly efficient in reversing the bone alterations in this HL rat model, which has proven to be useful for studying the fat–bone relationships.

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Short-term effect of alendronate on bone mass and bone remodeling in postmenopausal women

Osteoporosis International ◽

10.1007/bf01623003 ◽

1993 ◽

Vol 3 (S3) ◽

pp. 17-19 ◽

Cited By ~ 16

Author(s):

C. H. Chesnut ◽

S. T. Harris

Keyword(s):

Bone Mass ◽

Postmenopausal Women ◽

Bone Remodeling ◽

Term Effect ◽

Short Term ◽

Short Term Effect

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Therapeutic Potential of an Intestinotrophic Hormone, Glucagon-Like Peptide 2, for Treatment of Type 2 Short Bowel Syndrome Rats with Intestinal Bacterial and Fungal Dysbiosis

10.21203/rs.3.rs-512644/v1 ◽

2021 ◽

Author(s):

Xiuting Hu ◽

Wei Cheng ◽

Shengxian Fan ◽

Yuhua Huang ◽

Xi Chen ◽

...

Keyword(s):

Short Bowel Syndrome ◽

Relative Abundance ◽

Sham Group ◽

Therapeutic Potential ◽

Interaction Network ◽

Small Bowel Resection ◽

Its Sequencing ◽

Short Bowel ◽

Glucagon Like Peptide

Abstract Background: Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. Limited data are available for intestinal fungal dysbiosis. Moreover, no effective therapeutic drugs are available for these microbiota dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats.Methods: 8-week-old male SD rats which underwent 80% small bowel resection, ileocecum resection, partial colon resection and jejunocolostomy, were treated with saline (SBS group, n=5) or GLP-2 (GLP2.SBS group, n=5). The Sham group rats which underwent transection and re-anastomosis were given a saline placebo (Sham group, n=5). 16S rRNA and ITS sequencing were applied to evaluate the colonic bacterial and fungal composition at 22 days after surgery, respectively.Results: The relative abundance of Actinobacteria, Firmicutes and proinflammatory Proteobacteria increased significantly in SBS group rats, while the relative abundance of Bacteroidetes, Verrucomicrobia and Tenericutes decreased remarkably. GLP-2 treatment significantly decreased Proteus and increased Clostridium relative to the saline treated SBS rats. The diversity of intestinal fungi was significantly increased in SBS rats, accompanied with some fungi abnormally increased and some resident fungi (e.g., Penicillium) significantly decreased. GLP-2 treatment significantly decreased Debaryomyces and Meyerozyma, and increased Penicillium. Moreover, GLP-2 partially restored the bacteria-fungi interkingdom interaction network of SBS rats.Conclusion: Our study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.

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Abstract 13697: Glucagon-like Peptide-1 Analogue Liraglutide Does Not Improve Microvascular Myocardial Function in Patients With Type 2 Diabetes - a Randomized, Single-blinded Cross Over Trial

Circulation ◽

10.1161/circ.130.suppl_2.13697 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Rebekka Faber ◽

Mette Zander ◽

Adam A Pena ◽

Marie M Michelsen ◽

Naja D Mygind ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Systolic Blood Pressure ◽

Coronary Microcirculation ◽

Short Term ◽

Short Term Treatment ◽

Flow Reserve ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background: Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes. Methods: Twenty patients with type 2 diabetes and no history of coronary artery disease were treated with the GLP-1 analogue Liraglutide for 10 weeks, in a randomized single-blinded crossover setup. The effect of GLP-1 on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Data were analysed as two-sample t-test after ensuring no carry over effect. Results: A total of 20 patients (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45) completed full protocol. There was a small increase in CFR following GLP-1 treatment (change 0.18, CI95% [-0.01; 0.36], p=0.06) but with no difference in effect compared with the no treatment group (0.16, CI95% [-0.08; 0.40], p=0.18). GLP-1 significantly reduced glycated haemoglobin (-10.1 mmol/mol CI95% [-13.9; -6.4], p=<0.001) systolic blood pressure (-10 mmHg CI95% [-17; -3], p=0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p=0.03). Conclusion: Despite a significant weight-loss, reduction in HbA1c and systolic blood pressure, we did not find a significant improvement in coronary microcirculation after 10 weeks treatment with GLP-1. In our short-term treatment study, we therefore conclude that the GLP-1 analogue Liraglutide does not improve coronary microcirculation in patients with type 2 diabetes. Further long-term studies are needed to explore mechanisms to improve coronary microcirculation in patients with type 2 diabetes.

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