Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In clinical practice, exogenous pancreatic enzymes are administered for the treatment of pancreatogenic steatorrhea or with the intention to relieve pain due to chronic pancreatitis. Moreover, a large number of patients take pancreatin (i.e., exogenous pancreatic enzymes) for functional dyspepsia. The effect of exogenous pancreatic enzymes on the enteropancreatic axis is a complex issue. Intraduodenal but not intrajejunal protease activity appears to exert a dose-dependent negative feedback on exocrine pancreatic secretion. Only enzymes with a proteolytic activity but not amylase and lipase exert a control on pancreatic secretion. The mechanism responsible for this feedback regulation is debated, but the cholinergic system seems to play a major role. Intraduodenal pancreatic enzymes (pancreatin) lead to an increased release of pancreatic polypeptide but do not affect the release of insulin and glucagon. In addition, pancreatic enzymes have an influence on the release of some gastrointestinal hormones (i.e., cholecystokinin, motilin, gastric inhibitory polypeptide). Neither exogenous nor endogenous pancreatic enzymes seem to play a major role in the regulation of interdigestive gastrointestinal motility. However, an adequate rate of postprandial pancreatic output is required to control gastric emptying. Current knowledge on the effect of exogenous pancreatic enzymes on the enteropancreatic axis, gut peptide release and gastrointestinal motility are updated in the present article.
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PMID:Effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility. 822 68

A new surgical method of treating patients with unstable insulin-dependent diabetes (IDD) has been developed--that of surgically shunting pancreatic blood into the systemic blood flow with the purpose of creating a more optimal interaction of subcutaneously administered insulin and pancreas-secreted glucagon. The long term results of the operation depend on the patency of a splenorenal anastomosis. This has been studied by following up 137 patients over periods from half a year to three years. Anastomotic patency was determined by renal and splenic venography and celiacy arteriography, which revealed a patent anastomosis in 114 patients, and an obliterated one in 23. Patients with patent anastomoses showed a lowering of glycosylated hemoglobin (HbA1c) from 13.3 +/- 0.3% to 9.3 +/- 0.6%, p < 0.05, a decrease of the injected insulin dose from 0.97 +/- 0.04 to 0.72 +/- 0.03 U/kg, p < 0.05, disappearance or considerable abatement of pain in the lower extremities, and of hypoglycemia. Improvement of clinical status was accompanied by an increase of glucagon in the systemic blood stream from 60.8 +/- 10.1 to 91.5 +/- 9.4 pg/ml, p < 0.05, a rise of tissue oxygen pressure, pO2, from 49.2 +/- 2.4 to 58.1 +/- 1.9 mm Hg, p < 0.05. In patients with oblivious anastomoses postoperative HbA1c levels did not change from preoperative values: 12.9 +/- 0.4% and 12.8 +/- 0.7%, p < 0.05, respectively; the insulin dose remained the same--0.91 +/- 0.07 U/kg and 0.85 +/- 0.07 U/kg, p < 0.05, no rise of the systemic blood glucagon content was noted, and former complaints continued. The suggested method is not an alternative for insulin therapy, but considerably enhances its potential.
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PMID:Results of pancreatic blood shunting into the systemic blood flow in insulin-dependent diabetics. 880 78

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls (P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls (P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension (P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.
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PMID:Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome. 968 59

A 37-year-old male patient, without any particular symptoms apart from moderate right upper quadrant postprandial pain, was found to have a liver mass identified as a glucagon-producing tumor. Plasma glucagon levels were slightly increased, whereas those of other gut peptides were within the normal range. Despite an extensive pre- and intraoperative diagnostic work-up, a presumed primary glucagonoma remained undetected. This unusual presentation with the absence of any symptoms typical of glucagonoma, as well as the presence of histopathological features characteristic of both benign and malignant forms of glucagonoma, make this case very peculiar. A clinically silent, apparently unrelated adenocarcinoma of the left colon was also found. The concomitant presence of a glucagonoma and a carcinoma of the large intestine has not been previously reported, and its significance remains unclear.
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PMID:Asymptomatic glucagonoma presenting with an isolated hepatic nodule. 975 12

The central action of the peptide of intestinal tract, glucagon, was studied in Albino Swiss mice (20-25 g) and Wistar rats (200-220 g). Glucagon was injected intracerebroventricularly (icv) at the dose of 0.25, 0.5 and 1 microgram in 1 microliter of distilled water per mouse or 5 micrograms in 5 microliters per rat. It was found that glucagon administered icv increased glucose content in the peripheral blood serum. Behavioral studies have shown that glucagon diminished spontaneous locomotor activity in rats and mice, impaired exploratory activity and reduced amphetamine-induced hyperactivity. The results were not dependent on hyperglycaemia because the administration of 20% glucose solution po did not cause above effects. In addition, glucagon potentiated cataleptogenic effects of haloperidol. Icv injection of glucagon did not change the pain sensitivity or seizure susceptibility. The substance did not show the anxiolytic properties and did not affect the duration of hexobarbital-induced sleep. In biochemical studies it was found that glucagon injected icv induced the decrease in GABA content while the DA content was increased. The utilization of DA was not changed. The obtained results indicated, that glucagon injected icv exerted the central action, which was manifested by the central regulation of glucose level in the periphery. Moreover, glucagon inhibited the locomotor and exploratory activity as well as the amphetamine-induced hyperactivity and enhanced haloperidol-induced catalepsy. These effect could be connected with the inhibition of the central dopaminergic structures by glucagon.
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PMID:Central action of glucagon. 979 64

Somatostatin (SRIF, somatotropin release inhibiting factor), discovered for its inhibitory action on growth hormone (GH) secretion from pituitary, is an abundant neuropeptide. Two forms, SRIF14 and SRIF28 exist. Recently, a second family of peptides with very similar sequences and features was described; the cortistatins (CST), CST17 and CST29 which are brain selective. The five cloned SRIF receptors (sst1-5) belong to the G-protein coupled/ heptathelical receptor family. Structural and operational features distinguish two classes of receptors; SRIF1 - sst2/sst3/sst5 (high affinity for octreotide or seglitide) and SRIF2 = sst1/sst4(very low affinitty for the aforementioned ligands). The affinity of SRIF receptors for somatostatins and cortistatins is equally high, and it is not clear whether selective receptors do exist for one or the other of the peptides. Several radiologlands label all SRIF receptors, e.g., [125]LTT-SRIF28' [l25I]CGP23996, [125]Tyr10cortistatin or [125I]Tyr11SRIF14. In contrast, [125I]Tyr3octreotide, [125I]BIM23027, [125I]MK678 or [125I]D-Trp8SRIF14 label predominantly SRIF1 sites, especially sst2 and possibly sst5 receptors. In brain, [125I]Tyr3octreotide binding equates with sst2 receptor mRNA distribution. Native SRIF2receptors can be labeled with [125I]SRIF14 in the presence of high NaCl in brain (sst1) or lung (sst4) tissue. Short cyclic or linear peptide analogs show selectivity for sst2/sst5 (octreotide, lanreotide, BIM 23027), sst1 (CH-275), sst3 (sst3-ODN-8), or sst5 receptors (BIM 23268); although claims for selectivity have not always been confirmed. Beta peptides ith affinity for SRIF receptors are also reported. The general lack of SRIF receptor antagonists is unique for peptide receptors, although CYN 154806 is a selective and potent sst2 antagonist. Nonpeptide ligands are still rare, although a number of molecules have been reported with selectivity and potency for sst1 (L 757,519), sst2 (L 779,976), sst3 (L 796,778), sst4 (NNC 26-9100, L 803,087) or sst1/sst5 receptors (L 817,018). Such molecules are essential to establish the role of SRIF receptors, e.g., sst1 in hypothalamic glutamate currents: sst2 in inhibiting release of GH, glucagon, TSH, gastric acid secretion, pain, seizures and tumor growth, and sst5 in vascular remodeling and inhibition of insulin and GH release.
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PMID:Drug design at peptide receptors: somatostatin receptor ligands. 1193 45

PACAP and VIP are members of the VIP/secretin/glucagon family of peptides with neurotransmitter, neuroprotective, and neurotrophic functions. PACAP and VIP are known to be upregulated in primary sensory neurons following nerve injury, implying that these neuropeptides could be mediators of sensory transmission in neuropathic pain states. Nerve injury at the level of the trigeminal root is thought to be the prime cause of trigeminal neuralgia. Since cross-excitation (a chemically-mediated form of nonsynaptic transmission) within the TG is postulated to play a central role in trigeminal neuralgia, we studied the expression of PACAP and VIP receptors in the TG by RT PCR and immunocytochemistry. Of the three known receptors (PAC1, VPAC1 and VPAC2), RT PCR revealed the presence of mRNA for VPAC2 and several splice variants of the PAC1 receptor. Immunocytochemistry showed PAC1 and VPAC2 to be present in small-diameter TG neurons. Thus, PACAP and VIP are potential mediators of cross-excitation in the TG.
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PMID:Expression of VPAC2 receptor and PAC1 receptor splice variants in the trigeminal ganglion of the adult rat. 1222 67

Corticosteroids are considered to be essential stress hormones. They are secreted together with adrenocorticotropic hormone (ACTH) in response to the pulsatile secretion of corticotropin-releasing hormone from the paraventricular nucleus of the hypothalamus. Changes in pulse amplitude are responsible for the diurnal rhythm in circulating ACTH and cortisol levels. Steroid levels increase immediately after injury, pain, fever, and hypovolemia in response to the stimulation of corticotropin-releasing hormone secretion by various cytokines. The increase in steroid levels is typically proportional to the magnitude of stress, with serum cortisol values being highest in moribund patients and shortly before death. With severe and prolonged stress, steroid levels are increased for weeks to months and may be associated with hypertrophy of the adrenal cortex. Cortisol acts in concert with catecholamines to maintain the vascular tone, endothelial integrity, vascular permeability, and the distribution of total body water within the vascular compartment. It also potentiates the vasoconstrictor effects of catecholamines. Cortisol helps to stimulate lipolysis, inhibit protein synthesis, facilitate amino acid mobilization from muscle, induce the enzymes of gluconeogenesis, enhance secretion of glucagon, inhibit insulin secretion, and stimulate conversion of lactic acid to glycogen. Because of their anti-inflammatory properties, steroids have been proposed as therapeutic adjuvants in systemic inflammation and may protect the host against overshooting defense reactions by reducing the migration of leukocytes to the inflammatory sites and the incidence of neutrophil-mediated tissue injury and organ dysfunction.
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PMID:Steroids. 1238 86

About 15% of tumors of Langerhans, islets do not cause any hormone induced syndrome although they sintetise and secrete one or more regulatory peptides. These tumors are most frequently localised in the head and tail of the pancreas. They are usually greater then 5 cm. In diameter and present with pain, jaundice, palpable mass and malaise, rarely with variceal bleeding due to compression of the splenic vein. About 50% of the tumors present with symptoms caused by metastases. We present a 51 year old women in whom during the investigation for paraumbilical pain, predominantly on the left side a tumor of the tail of the pancreas was discovered and subsequently surgically removed. Standard histology showed a neuroendocrine tumor. Immunohistochemistry showed generalised immunoreactivity with antibodies against chromographin A, neuron specific enolasa and glucagon in more then 95% of cells. Somatostatatin was coexpressed in more then 5% of cells, PP in rare scattered cells. No reactivity was found for the other hormone markers. Ten years after surgery the patient has no signs of tumor recurrency.
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PMID:[Non-functioning tumor of the islets of Langerhans]. 1258 89

The current study aimed to refine the conventional distension model in the human rectum by measuring the cross-sectional area with a ramp-controlled impedance planimetric system. After preconditioning, the rectum in seven volunteers was distended 56 times with infusion rates of 50, 100 and 200 ml/min and at 100 ml/min during relaxation of the smooth muscle with glucagon. The pump was reversed at maximal tolerated pain. The subjects tolerated a higher volume and pressure with a more reliable sensory rating after preconditioning of the tissue. The three distension rates resulted in different pressure and tension at the maximal pain intensity (P < 0.02 and P < 0.05) with a decrease after relaxation of the smooth muscle with glucagon (P < 0.05). On the other hand, the cross-sectional area and volume were robust, did not show strain-rate dependency, and were not affected by muscle relaxation. Since the cross-sectional area is directly related to the deformation of the gut wall and hence to the strain, the study supports the idea that, independent of the muscular function, the mechano sensitive nociceptors in the human rectum depend directly on circumferential wall strain rather than on pressure and tension.
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PMID:Pain intensity and biomechanical responses during ramp-controlled distension of the human rectum. 1287 Jul 88


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