Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiological mechanisms responsible for diabetic gastroparesis remain unclear. Diabetes mellitus occurs spontaneously in 90% of a partially inbred colony of BB/W rats. This animal model resembles human insulin-dependent diabetes and is suitable for investigating the mechanism of diabetic gastroparesis. Diabetic BB/W rats were killed 6 mo after the onset of diabetes. Muscle contraction experiments and [3H]acetylcholine release studies were performed with muscle strips of the gastric body. Biochemical measurements of inositol trisphosphate (IP3) and protein kinase C (PKC) in gastric muscle were performed to characterize abnormalities of the intracellular signal transduction system in gastric myocytes. Circular muscle contractions in response to direct myogenic stimulants, carbachol (10(-7) - 10 (-3)M) or substance P (10(-7) - 10(-5)M), were significantly impaired in diabetic BB/W rats compared with controls. Similarly, muscle contractions in response to NaF (10 mM), a direct stimulant of G proteins, were also impaired in diabetic BB/W rats. In contrast, muscle contractions in response to KCl (25-75 mM) were similar between control and diabetic BB/W rats, indicating normal voltage-dependent Ca2+ entry in muscle strips obtained from diabetics BB/W rats. [3H]acetylcholine release from gastric myenteric plexus in response to electrical transmural stimulation remained intact in diabetic BB/W rats. In separate studies, we demonstrated that carbachol (10(-6) - 10(-4)M) -induced IP3 responses were significantly reduced in diabetic rats compared with control. In addition, there was also impairment of translocation of PKC in diabetic BB/W rats. These observations indicate that myogenic impairment occurred in diabetic BB/W rats. This resulted from altered intracellular signal transduction involving abnormal IP3 production and PKC translocation.
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PMID:Impaired intracellular signal transduction in gastric smooth muscle of diabetic BB/W rats. 863 6

Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in developed and developing nations and over 50% of patients with prolonged stages of disease experience forms of autonomic neuropathy. These patients have symptoms indicating disrupted enteric nervous system function including gastric discomfort, gastroparesis and intestinal dysmotility. Previous assessments have examined enteric neuronal injury within either type 1 diabetic or transgenic type 2 diabetic context. This study aims to assess damage to myenteric neurons within the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2 diabetes, as this disease context is most parallel to the human condition and disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After 8 weeks, the total number of duodenal myenteric neurons and the synaptophysin density index were reduced and transmission electron microscopy showed axonal swelling and loss of neurofilaments and microtubules, suggesting compromised neuronal health. High-fat diet ingestion correlated with a loss of neurons expressing VIP and nNOS but did not affect the expression of ChAT, substance P, calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those with inhibitory nature. This pathology may underlie dysmotility and other negative GI symptoms experienced by human type 2 diabetic and obese patients.
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PMID:High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes. 2388 4