Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans

Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) upregulates hepatic insulin sensitivity. Recently, contact sites between the endoplasmic reticulum and mitochondria named mitochondria-associated membranes (MAMs) emerged as a crucial hub for insulin signaling in the liver. As mitochondria are targets of NO, we explored whether NO regulates hepatic insulin sensitivity by targeting MAMs. In Huh7 cells, primary rat hepatocytes and mouse livers, enhancing NO concentration increased MAMs, whereas inhibiting eNOS decreased them. In vitro, those effects were prevented by inhibiting protein kinase G (PKG) and mimicked by activating soluble guanylate cyclase (sGC) and PKG. In agreement with the regulation of MAMs, increasing NO concentration improved insulin signaling, both in vitro and in vivo, while eNOS inhibition disrupted this response. Finally, inhibition of insulin signaling by wortmannin did not affect the impact of NO on MAMs, while experimental MAM disruption, using either targeted silencing of cyclophilin D or the overexpression of the organelle spacer fetal and adult testis-expressed 1 (FATE-1), significantly blunted the effects of NO on both MAMs and insulin response. Therefore, under physiological conditions, NO participates to the regulation of MAM integrity through the sGC/PKG pathway and concomitantly improves hepatic insulin sensitivity. Altogether, our data suggest that the induction of MAMs participate in the impact of NO on hepatocyte insulin response.

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1074 Gallstone Ileus: Two Decades After Cholecystectomy

British Journal of Surgery ◽

10.1093/bjs/znab259.358 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

K Matwala ◽

M R Iqbal ◽

T Shakir ◽

D W Chicken

Keyword(s):

Small Bowel ◽

Bowel Obstruction ◽

Rare Complication ◽

Open Cholecystectomy ◽

Gallstone Ileus ◽

Proximal Small Bowel ◽

Solid Diet ◽

History Of ◽

Ileocaecal Junction ◽

Tomography Scan

Abstract Introduction Gallstone ileus is a rare complication of gallstones that occurs in 1%-4% of all cases of bowel obstruction. We present a surprising case of gallstone ileus causing small bowel obstruction 19 years after open cholecystectomy. Case Report A 77-year-old male presented with a 3-day history of abdominal pain, 4 episodes of vomiting and absolute constipation. He had a surgical background of an open cholecystectomy and open appendicectomy 19 years and 45 years ago respectively. Medically, he had well-controlled hypertension and experienced a TIA 5 years prior. Computed Tomography Scan of the abdomen and pelvis revealed features consistent with an obstructing, heterogenous opacity in the distal small bowel without pneumobilia. The patient subsequently underwent diagnostic laparoscopy. Intraoperatively, an obstructing gallstone, measuring 4 cm, was found 50cm proximal to the ileocaecal junction, with dilatation of the proximal small bowel and distal collapse. Enterotomy and removal of the stone was done. Post-operatively, this gentleman recovered without complications and was discharged home two days later after being able to tolerate a solid diet. Conclusions This is the second reported case of gallstone ileus in a patient with previous cholecystectomy about two decades ago, according to our literature search. Although extremely rare, absence of the gallbladder does not exclude the possibility of gallstone ileus.

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Small intestinal motility in fasted and postprandial states: effect of transient vagosympathetic blockade

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.252.3.g301 ◽

1987 ◽

Vol 252 (3) ◽

pp. G301-G308 ◽

Cited By ~ 4

Author(s):

S. A. Chung ◽

N. E. Diamant

Keyword(s):

Small Bowel ◽

Intestinal Motility ◽

Gastric Fundus ◽

Phase Iii ◽

Entire Small Bowel ◽

Vagal Blockade ◽

Small Intestinal Motility ◽

Proximal Small Bowel ◽

Small Intestinal ◽

Gastric Contractions

We investigated vagal control of the migrating myoelectric complex (MMC) and postprandial pattern of the canine small intestine. Gastric and small intestinal motility were monitored in six conscious dogs. The vagosympathetic nerves, previously isolated in bilateral skin loops, were blocked by cooling. To feed, a meat-based liquid food was infused by tube into the gastric fundus. MMC phases I, II, III, and IV were observed in the fasted state. On feeding, the fed pattern appeared quickly in the proximal small bowel but was delayed distally. Vagal blockade abolished all gastric contractions and spiking activity as well as the small bowel fed pattern. During vagal blockade, the small bowel exhibited MMC-like migrating bursts of spikes in both the fasted and fed states. The migration and cycling of these bursts were not significantly different from the MMC, but the duodenal and jejunal phase II was absent or shortened. On termination of vagal blockade, normal fasting or fed activity reappeared but with a delay in the fed pattern distally. We conclude: the ileum is the least sensitive to vagal blockade; the fasting vagal influence is exerted primarily on phases I and II of the duodenal and jejunal MMC; the fed pattern throughout the entire small bowel is normally dependent upon vagal integrity; the phase III-like bursts of activity seen during vagal blockade likely represents the intrinsic small bowel MMC, which is vagally independent.

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