Sstr5^−/− mice had increased circulating GLP-1 levels along with decreased nonfasted glucose and insulin levels, and lacked S5A1-stimulated GLP-1 secretion. Nonfasted (a) GLP-1, (b) glucose, and (c) insulin in Sstr5^−/− mice compared with WT littermates at 7 to 15 weeks of age. (d) Nonfasted active GLP-1 levels in Sstr5^−/− mice at 19 months of age compared with WT littermates. (e) Effects of S5A1 in Sstr5^−/− mice and WT littermates on overnight-fasted active GLP-1 levels (n = 5 to 6 per group). Data shown as mean ± standard error of the mean. *P < 0.05; **P < 0.01; ***P < 0.001.