Stimulating intestinal GIP release reduces food intake and body weight in mice.

OBJECTIVE: Glucose dependent insulinotropic polypeptide (GIP) is well established as an incretin hormone, boosting glucose-dependent insulin secretion. However, whilst anorectic actions of its sister-incretin glucagon-like peptide-1 (GLP-1) are well established, a physiological role for GIP in appetite regulation is controversial, despite the superior weight loss seen in preclinical models and humans with GLP-1/GIP dual receptor agonists compared with GLP-1R agonism alone. METHODS: We generated a mouse model in which GIP expressing K-cells can be activated through hM3Dq Designer Receptor Activated by Designer Drugs (DREADD, GIP-Dq) to explore physiological actions of intestinally-released GIP. RESULTS: In lean mice, Dq-stimulation of GIP expressing cells increased plasma GIP to levels similar to those found postprandially. The increase in GIP was associated with improved glucose tolerance, as expected, but also triggered an unexpected robust inhibition of food intake. Validating that this represented a response to intestinally-released GIP, the suppression of food intake was prevented by injecting mice peripherally or centrally with antagonistic GIPR-antibodies, and was reproduced in an intersectional model utilising Gip-Cre/Villin-Flp to limit Dq transgene expression to K-cells in the intestinal epithelium. The effects of GIP cell activation were maintained in diet induced obese mice, in which chronic K-cell activation reduced food intake and attenuated body weight gain. CONCLUSIONS: These studies establish a physiological gut-brain GIP-axis regulating food intake in mice, adding to the multi-faceted metabolic effects of GIP which need to be taken into account when developing GIPR-targeted therapies for obesity and diabetes.

Clinical progression of patients with COVID-19 in Lagos State, Nigeria.

BACKGROUND: The majority of COVID-19 research has been devoted to characterizing the epidemiology and early clinical aspects of the virus. In Lagos, Nigeria, we looked at the temporal progression of COVID-19 patients. We included 1337 confirmed COVID-19 cases in our study from February 27th to March 27th 2020. Of the 1337 patients enrolled, the median age was 50 years old, and 800 (59.83%) were male while 537 (40.16%) were female. METHOD: In symptomatic patients, the time from the beginning of signs to admission was 4 (2-7) days. Fever occurred in 217 (16.2%) while cough occurred in 211(15.78%) patients respectively. Patients were given 5-6 treatment, including nutrition support, supplementary oxygen, and antiviral medicines (e.g., Remdesivir, dexamethasone) in a limited percentage of cases. The assessed median period of infection in all patients was 10 days after the start of symptoms (95 confidential intervals [CIs]: 8-11 days). The duration of fever was slightly longer in patients admitted to intensive care units (ICU) than in those who were not (31 days versus 9 days, respectively, P < 0.003). RESULTS: On day 7 after the onset of symptoms, radiological deterioration of the original picture was found in 500 (37.39%) patients. On day 13, 154 of these patients (94.5%) showed signs of radiological improvement. The average time it took for upper respiratory tract samples to test negative for reverse transcriptase PCR was 10 days (90 percent confidence interval: 10-12 days). Virus clearance was more significant in ICU patients than in non-ICU patients (P < 0.003). CONCLUSIONS: Community members should continue to adhere to the recommended methods of preventing the spread of COVID-19 infection and patients should seek care early to reduce the risk of mortality associated with the infection as rapidly as possible.