Diabetogia: Can selective stimulation of colon L cells improve metabolic outcomes in mice?

!---- insulin-like peptide-5 (INSL5) is present only in the far end l cells of the colon and is expressed in combination with glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).and GLP-1 and PYY are anorexia, while INSL5 is considered carcinogenic.we aim to clarify the metabolic effects of selective stimulation of distant colon L cells in mice.the insl5 promoter-driven gq conjugate dating design receptor (DREADD) expressed by the Insl5 promoter to activate the far-end colon L cell (Ldistal Dq).evaluate IPGTT and food intake in the event of DREADD activation and inactivation, respectively.use of chlor-nitrogen flat N-oxides (CNO; 0.3 mg / kg i.p.) to stimulate LdistalDq cells to increase plasma GLP-1 and PYY (2.67 and 3.31 times, respectively);IPGTT (2 g / kg body weight) showed a significant improvement in glucose tolerance after injection of CNO.CNO-treated mice also showed reduced food intake and weight loss after 24 hours, and bowel feces increased, the latter sensitive to 5-serotonin (5-HT) receptor 3 inhibition.the use of GLP1 receptor blocking antibody pretreatment, neutralized the improvement of CNO glucose tolerance, but did not affect the reduction of food intake, independent groups of animals on the feeding CNO treatment group, the weight loss was significant.pretreatment with the neuropeptide Y receptor type 2 antagonist JNJ-3102028 eliminated CNO's dependence on food intake.'s assessment of systemic physiology in metabolic cages showed that LdistalDq cell stimulation increased energy consumption and increased activity.high-fat diet for 2 weeks, it is enough to maintain acute CNO-induced food intake and glucose steady state.this proof-of-concept study shows that selective far-end colon L cell stimulation has beneficial metabolic results..