The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

The incidence of CRC was not significantly higher in our veteran patients with IBD than in control patients in the general VA population. In contrast, our IBD patients had a significantly higher risk for extracolonic cancers than controls, including cancers of the skin, kidneys, prostate, and pancreas. 10.1093/ibd/izx046_video1Video 1.izx046_Mosher_Video5734484616001.

PRESENTATIONA 34-year-old Hispanic man with a history of alcoholic cirrhosis and type 2 diabetes mellitus presented with 2 weeks of diarrhea, nausea, vomiting, abdominal pain, rash, and syncope. Five days before presentation he developed an erythematous petechial rash on his right hand that spread sequentially to his left hand, forearms, feet, legs, and flanks. The rash was neither pruritic nor painful, and he denied prior history of a rash. He reported no recent infections or antibiotic use. His past medical history was negative for connective tissue disease and was otherwise noncontributory. There were no other significant findings upon review of systems. ASSESSMENTOn admission, the patient was afebrile, hypotensive (82/69 mm Hg), and tachycardic (104 beats per minute), which resolved after normal saline boluses. Physical examination was significant for petechiae on the hard palate and diffuse palpable petechiae in the distribution described above ( Figure 1A and B). His examination was otherwise notable for right elbow erythema and purulent drainage. Laboratory serologies were negative for human immunodeficiency virus, hepatitis B and C, and rheumatoid factor. Other laboratory findings included low serum complement component 3 (C3), negative antimyeloperoxidase antibodies, and positive perinuclear antineutrophil cytoplasmic antibodies.Two of 4 blood cultures and a wound culture from the purulent elbow site were positive for methicillin-sensitive Staphylococcus aureus (MSSA). A transthoracic echocardiogram was negative for vegetations. A punch skin biopsy of the rash showed an infiltrate of lymphocytes, histiocytes, neutrophils, and eosinophils with minimal fibrin deposition in blood vessel walls (Figure 2). Direct immunofluorescence was positive for immunoglobulin G and C3 deposition with trace immunoglobulin A in the walls of papillary dermal vessels. These findings were consistent with early leukocytoclastic vasculitis.

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