Analysis of Gly40Ser polymorphism of the glucagon receptor (GCGR) gene in different ethnic groups

Barbato, Antonio; Russo, Paola; Venezia, Antonella; Strazzullo, Viviana; Siani, Alfonso; Cappuccio, Francesco P.

doi:10.1038/sj.jhh.1001591

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…Enhanced proximal tubular sodium reabsorption and a higher prevalence of hypertension have been associated with the Gly40Ser polymorphism of the GCGR gene resulting in a mutated receptor less responsive to glucagon (Strazzullo et al . 2001, Barbato et al . 2003).…”

Section: Other Actions Of Oxmmentioning

confidence: 99%

Unraveling oxyntomodulin, GLP1's enigmatic brother

Pocai¹

2012

Journal of Endocrinology

118

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Oxyntomodulin (OXM) is a peptide secreted from the L cells of the gut following nutrient ingestion. OXM is a dual agonist of the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) combining the effects of GLP1 and glucagon to act as a potentially more effective treatment for obesity than GLP1R agonists. Injections of OXM in humans cause a significant reduction in weight and appetite, as well as an increase in energy expenditure. Activation of GCGR is classically associated with an elevation in glucose levels, which would be deleterious in patients with T2DM, but the antidiabetic properties of GLP1R agonism would be expected to counteract this effect. Indeed, OXM administration improved glucose tolerance in diet-induced obese mice. Thus, dual agonists of the GCGR and GLP1R represent a new therapeutic approach for diabetes and obesity with the potential for enhanced weight loss and improvement in glycemic control beyond those of GLP1R agonists.

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Section: Other Actions Of Oxmmentioning

confidence: 99%

Unraveling oxyntomodulin, GLP1's enigmatic brother

Pocai¹

2012

Journal of Endocrinology

118

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“…A polymorphic variant of the glucagon receptor gene has been described. It is the result of a missense mutation leading to the substitution of a serine for a glycine in the encoded protein (Gly40Ser) (Shiota et al 2002;Barbato et al 2003). This variant is present in 1-3% of Caucasian populations.…”

Section: Introductionmentioning

confidence: 99%

Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis

et al. 2018

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Plasma potassium concentration (PK) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. Previous studies in rats showed that glucagon infusion increased urinary potassium excretion dose‐dependently and reversibly. This prompted us to investigate the possible influence of glucagon on potassium handling in humans. We took advantage of the Gly40Ser mutation of the glucagon receptor (GR) that results in a partial loss of function of the GR. In the Olivetti cohort (male workers), 25 subjects who carried this mutation were matched 1:4 to 100 noncarriers for age and weight. Estimated osmolarity of serum and 24‐h urine (Sosm and Uosm, respectively) was calculated from the concentrations of the main solutes: [(Na+K)*2 + urea (+glucose for serum)]. Transtubular potassium gradient (TTKG), reflecting the intensity of K secretion in the distal nephron, was calculated as [(urine K/serum K)(Uosm/Sosm)]. There was no significant difference in serum K, or 24‐h urine urea, Na and K excretion rates. But urine K concentration was significantly lower in carriers than in noncarriers. Means (interquartile range): 38 (34–43) versus 47 (43–51) mmol/L, P = 0.030. TTKG was also significantly lower in carriers: 4.2 (3.9–4.6) versus 5.0 (4.7–5.2), P = 0.015. This difference remained statistically significant after adjustments for serum insulin and 24‐h Na and urea excretions. These results in humans suggest that glucagon stimulates K secretion in the distal nephron. Thus, in conjunction with insulin, glucagon may also participate in K homeostasis by promoting renal K excretion.

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Nonpharmacologic Management of Hypertension

Stranges¹,

Cappuccio²

2007

Comprehensive Hypertension

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Analysis of Gly40Ser polymorphism of the glucagon receptor (GCGR) gene in different ethnic groups

Cited by 5 publications

References 22 publications

Unraveling oxyntomodulin, GLP1's enigmatic brother

Unraveling oxyntomodulin, GLP1's enigmatic brother

Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis

Nonpharmacologic Management of Hypertension

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