Gastric inhibitory polypeptide immunoneutralization attenuates development of obesity in mice

Boylan, Michael O.; Glazebrook, Patricia A.; Tatalovic, Milos; Wolfe, M. Michael

doi:10.1152/ajpendo.00345.2015

Cited by 54 publications

(39 citation statements)

References 46 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that weight gain, subcutaneous and visceral fat mass, cancellous bone mineral density, bone cortical thickness, and plasma osteocalcin levels were reduced in GIP knockout mice compared with WT mice. These results are consistent with previous findings in GIP receptor knockout mice, GIP receptor antagonists, chemical K‐cell ablation, and GIP antibody therapy showing the anabolic effect of GIP on adipose tissue and bone.…”

Section: Discussionsupporting

confidence: 93%

Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice

Shimazu-Kuwahara

Kanemaru

Harada

et al. 2018

J of Diabetes Invest

View full text Add to dashboard Cite

Given the established roles of glucose‐dependent insulinotropic polypeptide (GIP) in promoting fat storage and bone formation, we assessed the contribution of GIP to obesity and osteopenia in ovariectomized mice with a gene encoding green fluorescent protein (GFP) inserted into the GIP locus, in which GIP was either reduced (GIP gfp/+ ) or absent (GIP gfp/gfp ). In GIP gfp/gfp mice, weight gain, subcutaneous and visceral fat mass were reduced, and glucose intolerance was improved compared with wild‐type mice with the same magnitude of insulin responses. Cancellous bone mineral density and bone cortical thickness were reduced in GIP gfp/gfp mice compared with wild‐type mice. In GIP gfp/+ mice, weight gain, glucose intolerance and cancellous bone mineral density were not different from that of wild‐type mice. These results indicate that the total elimination of GIP ameliorates weight gain and adiposity in ovariectomized mice, but it enhances osteopenia, particularly in cancellous bone by partly suppressing bone formation.

show abstract

Section: Discussionsupporting

confidence: 93%

Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice

Shimazu-Kuwahara

Kanemaru

Harada

et al. 2018

J of Diabetes Invest

View full text Add to dashboard Cite

show abstract

“…These results are in line with GWAS studies identifying GIPR-E354 major allele as a risk factor for obesity (Berndt et al, 2013;Graff et al, 2017). GIPR knockout mice are resistant to dietinduced obesity identifying a role for GIPR in regulation of body weight (Boylan et al, 2015;Miyawaki et al, 2002). The focus of our studies were on β-cells, and β-cellspecific ablation of GIPR mice does not prevent against diet induced obesity (Campbell et al, 2016), suggesting that β-cell GIPR alone is not sufficient to understand the mechanism of weight gain in these mice.…”

Section: Discussionsupporting

confidence: 87%

“…In GIPR based therapy, there is a dichotomy between agonism and antagonism of the receptor (Khan et al, 2020;Killion et al, 2020). Studies have targeted either GIP (Barbosa-Yañez et al, 2019;Boylan et al, 2015) or GIPR (Killion et al, 2018) with antagonist antibodies and have revealed a protective effect against dietinduced body weight gain. Others have used GIPR peptide agonists to show that by chronically infusing either GIP analog (Mroz et al, 2019) or by a dual treatment with a GLP-1 analog (Finan et al, 2013), a decreased weight and metabolic benefits can be achieved.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal regulation of GIPR signaling impacts glucose homeostasis as revealed in studies of a common GIPR variant

Yammine

Picatoste

Abdullah

et al. 2020

Preprint

View full text Add to dashboard Cite

Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone, has a role in controlling postprandial metabolic tone. A GIP receptor (GIPR) variant (Q354, rs1800437) is associated with enhanced glucose tolerance and a lower BMI. To isolate the contribution of GIPR in metabolic control, we generated a mouse model of the GIPR-Q354 variant. Islets isolated from both male and female GIPR-Q variant mice have an enhanced glucose sensitivity and enhanced GIP response. In whole animal studies only female GIPR-Q variant mice are more glucose tolerant, whereas males have normal glucose tolerance but an enhanced sensitivity to GIP. In both sexes postprandial GIP levels are reduced, revealing feedback between the sensitivity of GIP target tissues and the secretion of GIP from intestinal endocrine cells. In line with the association of the variant with reduced BMI, GIPR-Q350 mice are resistant to dietinduced obesity. GIPR, a GPCR, is coupled to elevated cAMP. Prior studies have established altered post-activation traffic of the GIPR-Q variant without a change in affinity for GIP or in cAMP production. Consequently, our data link altered intracellular traffic of the GIPR-Q variant with GIP metabolic control of metabolism. Incretin hormone action is targeted in treatment of insulin-resistance, and our findings support pharmacologic targeting the GIPR to mimic the altered trafficking of the GIPR-Q variant as a potential strategy to enhance GIP metabolic effects in treatment of insulin resistance.

show abstract

“…GIP plays an important role in high-fat diet (HFD)-induced obesity and insulin resistance (Harada et al 2008. Previous studies using GIP immunoneutralization, GIPRknockout mice, and GIPR antagonists reported that inhibition of GIP signaling ameliorates HFD-induced obesity and insulin resistance (Miyawaki et al 2002, McClean et al 2008, Boylan et al 2015. HFD strongly stimulates GIP secretion (Iwasaki et al 2015, Murata et al 2019, and inhibition of GIP secretion also alleviates HFD-induced obesity and insulin resistance (Nasteska et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Absence of GIP secretion alleviates age-related obesity and insulin resistance

Kanemaru

Harada

Shimazu-Kuwahara

et al. 2020

Journal of Endocrinology

View full text Add to dashboard Cite

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin secreted from enteroendocine K cells after nutrient ingestion. Fat strongly induces GIP secretion, and GIP hypersecretion is involved in high-fat diet-induced obesity and insulin resistance. Aging also induces GIP hypersecretion, but its effect on body weight gain and insulin sensitivity remains unclear. In the present study, we investigated the effect of GIP on age-related body weight gain and insulin resistance using GIP-knockout homozygous (GIP−/−) and heterozygous (GIP+/−) mice, which have entirely absent and 50% reduced GIP secretion compared to wild-type (WT) mice, respectively. Under 12% fat-containing normal diet feeding condition, body weight was significantly lower in GIP−/− mice compared to that in WT and GIP+/− mice from 38 weeks of age, while there was no significant difference between WT and GIP+/− mice. Visceral and s.c. fat mass were also significantly lower in GIP−/− mice compared to those in WT and GIP+/− mice. During oral glucose tolerance test, blood glucose levels did not differ among the three groups. Insulin levels were significantly lower in GIP−/− mice than those in WT and GIP+/− mice. During insulin tolerance test, GIP−/− mice showed higher insulin sensitivity than that of WT and GIP+/− mice. Adiponectin mRNA levels were increased and leptin mRNA levels tended to be decreased in adipose tissue of GIP−/− mice. These results demonstrate that GIP is involved in age-related obesity and insulin resistance and that inhibition of GIP secretion alleviates age-related fat mass gain and insulin resistance under carbohydrate-based diet feeding condition.

show abstract

Gastric inhibitory polypeptide immunoneutralization attenuates development of obesity in mice

Cited by 54 publications

References 46 publications

Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice

Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice

Spatiotemporal regulation of GIPR signaling impacts glucose homeostasis as revealed in studies of a common GIPR variant

Absence of GIP secretion alleviates age-related obesity and insulin resistance

Contact Info

Product

Resources

About