Combined gastrin releasing peptide-29 and glucagon like peptide-1 reduce body weight more than each individual peptide in diet-induced obese male rats

Mhalhal, Thaer R.; Washington, Martha C.; Newman, Kayla D.; Heath, John; Sayegh, Ayman I.

doi:10.1016/j.npep.2017.11.009

Cited by 7 publications

(3 citation statements)

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“…These observations have been corroborated by human trials, in which treatment with human recombinant GRP (hrGRP) led to weight loss through reduced food intake (31). In summary, our results motivate investigations into hrGRP for appetite control and body weight lowering to possibly assist in T2D management and remission, an approach similar to recently implemented treatment strategies targeting incretins, like GLP-1, and associated receptors, with preliminary evidence of an additive effect in rats (32). Several T2D loci have been reported to be specific to certain ancestries (23)(24)(25).…”

Section: From Genome To Phenome Via the Proteomesupporting

confidence: 72%

From genome to phenome via the proteome: broad capture, antibody-based proteomics to explore disease mechanisms

Koprulu

Carrasco-Zanini

Wheeler

et al. 2022

Preprint

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Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify disease causing genes and proteins and to improve our understanding of the underlying mechanisms. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using novel antibody-based assays (Olink ® Explore 1536 and Explore Expansion) to identify disease causing genes and proteins across the human phenome. We describe 1,553 distinct credible sets of protein quantitative trait loci (pQTL), of which 256 contained cis-pQTLs not previously reported. We identify 224 cis-pQTLs shared with 578 unique health outcomes using statistical colocalization, including, gastrin releasing peptide (GRP) as a potential therapeutic target for type 2 diabetes. We observed convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for twelve protein coding genes (e.g., TIMD4 and low-density lipoprotein metabolism), highlighting the complementary nature of both approaches for drug target prioritization. Proteogenomic evidence also improved causal gene assignment at 40% (n=192) of overlapping GWAS loci, including DKKL1 as the candidate causal gene for multiple sclerosis. Our findings demonstrate the ability of broad capture, high-throughput proteomic technologies to robustly identify new gene-protein-disease links, provide mechanistic insight, and add value to existing GWASs by enabling and refining causal gene assignment.

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Section: From Genome To Phenome Via the Proteomesupporting

confidence: 72%

From genome to phenome via the proteome: broad capture, antibody-based proteomics to explore disease mechanisms

Koprulu

Carrasco-Zanini

Wheeler

et al. 2022

Preprint

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“…Therefore, the actions of NS CCK-8, possibly including reduction of food intake, may be peripheral/local i.e., gastrointestinal. Others (Calingasan et al, 1992;Cox et al, 1996;Smith et al, 1988) and we (Mhalhal et al, 2017b;Newman et al, 2017;Sayegh et al, 2015;Washington et al, 2016b) have shown that the gastrointestinal tract is a potential site of action for reduction of food intake by S CCK-8, GRP-29 and GLP-1, (Mhalhal et al, 2017a(Mhalhal et al, , 2018Washington et al, 2014), because intra-arterial infusions of S CCK-8 (0.05 nmol/kg) in the cranial mesenteric artery, which supplies the small intestine, but not ip injections, reduced food intake (Mhalhal et al, 2017a,b;Sayegh et al, 2015;Washington et al, 2016a,b). In addition, interrupting the enteric neurons utilizing a duodenal myotomy procedure also attenuated reduction of food intake by the same peptide (Lateef et al, 2012).…”

Section: Discussionmentioning

confidence: 89%

Non-sulfated cholecystokinin-8 increases enteric and hindbrain Fos-like immunoreactivity in male Sprague Dawley rats

et al. 2019

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Recently, we reported that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake by cholecystokinin-B receptors (CCK-BR). To examine a possible site of action for this peptide, and based on the fact that both NS CCK-8 and CCK-BR are found centrally and peripherally, in the current study we hypothesized that NS CCK-8 increases Fos-like immunoreactivity (Fos-LI, a neuronal activation marker) in the dorsal vagal complex (DVC) of the hindbrain and the myenteric and submucosal plexuses of the small intestine. We found that intraperitoneal NS CCK-8 (0.5 nmol/kg) increases Fos-LI in the DVC, the myenteric and the submucosal plexuses of the duodenum and the myenteric plexus of the jejunum. The findings suggest, but does not prove, a potential role for the DVC and the enteric neurons in the feeding responses evoked by NS CCK-8.

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“…GLP-1 receptor agonists promote the secretion of GLP-1 by binding to the receptor, thereby producing a hypoglycemic effect[ 16 ]. MGP is a strong inhibitor of calcium and phosphorus deposition that can bind to bone morphogenetic protein-2 to inhibit its biological activity and affect the transformation of mesenchymal cells into chondrocytes or osteoid cells[ 17 - 20 ]. In this study, serum GLP-1 and MGP levels were compared among the three groups.…”

Section: Discussionmentioning

confidence: 99%

Significance of serum glucagon-like peptide-1 and matrix Gla protein levels in patients with diabetes and osteoporosis

Xie¹,

Zhang²,

Hu³

et al. 2022

WJCC

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BACKGROUND Osteoporosis is a systemic bone disease characterized by decreased bone mass, impaired bone mass, and reduced bone strength that leads to increased bone fragility and fracture. Type 2 diabetes mellitus (T2DM) complicated with osteoporosis is a common systemic metabolic bone disease, and reduced bone mass and bone strength are considered the main clinical features; however, the pathogenesis of this disease has not been fully clarified. Its occurrence is considered related to sex, age, and genetic factors. There are many risk factors for diabetes complicated with osteoporosis. Therefore, exploring these risk factors will help prevent it. AIM To investigate the relationships among serum glucagon-like peptide-1 (GLP-1) levels, matrix Gla protein (MGP) levels, and diabetes with osteoporosis. METHODS Sixty patients with T2DM complicated with osteoporosis confirmed by the endocrinology department of our hospital were selected as the case group. Sixty T2DM patients with bone loss were selected as the control group. Sixty healthy participants were selected as the healthy group. The general data, bone mineral density index, and bone metabolic markers of the three groups were compared. The relationships among GLP-1 levels, MGP levels, and the bone mineral density index of the case group were analyzed using linear correlation analysis and a logistic regression model. RESULTS Differences in sex, smoking, and drinking among the case group, control group, and healthy group were not statistically significant ( P > 0.05). The mean age of the case group was older than those of the control and healthy groups ( P < 0.05). The body mass index, fasting plasma glucose level, HbA1c level, hypertension rate, and coronary heart disease rate of the case and control groups were higher than those of the healthy group ( P < 0.05). The serum GLP-1 and MGP levels of the case group were lower than those of the control and healthy groups; these differences were statistically significant ( P < 0.05). The serum GLP-1 and MGP levels of the control group were lower than those of the healthy group; these differences were statistically significant ( P < 0.05). The serum GLP-1 and MGP levels of the case group were significantly positively correlated with the bone mineral density values of the hip and lumbar spine ( P < 0.05). The results of the logistic regression model showed that age and duration of diabetes were independent risk factors for osteoporosis in diabetic patients ( P < 0.05) and that increased GLP-1 and MGP values were protective factors against osteoporosis in diabetic patients ( P < 0.05). CONCLUSION Serum GLP-1 and MGP levels of diabetic patients with osteoporosis were significantly ...

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Combined gastrin releasing peptide-29 and glucagon like peptide-1 reduce body weight more than each individual peptide in diet-induced obese male rats

Cited by 7 publications

References 50 publications

From genome to phenome via the proteome: broad capture, antibody-based proteomics to explore disease mechanisms

From genome to phenome via the proteome: broad capture, antibody-based proteomics to explore disease mechanisms

Non-sulfated cholecystokinin-8 increases enteric and hindbrain Fos-like immunoreactivity in male Sprague Dawley rats

Significance of serum glucagon-like peptide-1 and matrix Gla protein levels in patients with diabetes and osteoporosis

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