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)

Cyclosporin (CYA) was administered to Wistar rats at immunotherapeutic doses (20 mg/kg) and the functional and morphological effects on pancreatic B cells were observed. Serum CYA levels were kept in the range that is often encountered in clinical immunotherapy in humans. The treated rats had slightly elevated plasma glucose levels; on treatment days 6 and 13, their serum immunoreactive insulin and pancreatic insulin contents were low. Plasma immunoreactive glucagon levels were slightly elevated during treatment. Glucose tolerance was impaired on day 13. These functional abnormalities disappeared 2 weeks after drug withdrawal. B cells showed ultrastructural evidence of CYA toxicity, including cytoplasmic degranulation, nuclear inclusions, and cisternal dilatation of both the rough endoplasmic reticulum and the Golgi apparatus. These changes were observed on the third day of treatment and became more pronounced on the 6th and 13th days of treatment. By the second week after drug withdrawal, most of the B cells presented a normal ultrastructure. We confirmed that a dose of CYA similar to that used in clinical immunotherapy in humans produces ultrastructural disturbances in the pancreatic B cells of Wistar rats after relatively short-term administration.
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PMID:Ultrastructural and functional studies of pancreatic B cells in Wistar rats treated with immunotherapeutic doses of cyclosporin. 304 79

The effect of antihypertensive therapy with guanabenz or hydrochlorothiazide (HCTZ) on the secretion of growth hormone, prolactin, insulin, and glucagon was evaluated in double-blind fashion in 45 patients. Fifteen patients were treated with HCTZ, 50 mg twice daily, and 30 patients were treated with twice-daily dosages of guanabenz ranging from 4 to 32 mg. Blood samples for hormone analysis were collected during maintenance therapy when blood pressure was controlled as well as 1 week after the withdrawal of the antihypertensive medications. Serum levels of growth hormone and prolactin were within the normal ranges and were unchanged during treatment with HCTZ or guanabenz at any dose level. Interpatient variability in insulin levels was high, although within-subject insulin levels generally were consistent. No treatment effects were seen for insulin levels among guanabenz- or HCTZ-treated patients. Glucagon levels generally were above the expected range for fasting patients and were lower in patients receiving 4 or 8 mg of guanabenz twice daily than in those receiving 16 mg twice daily (p less than 0.05) and in those treated with HCTZ (p less than 0.01). However, analysis of paired data revealed no changes in glucagon levels upon withdrawal of guanabenz, whereas glucagon levels were higher during HCTZ treatment than after drug withdrawal (p = 0.012). Since guanabenz treatment did not affect the secretion of pancreatic or pituitary hormones, it may be preferable to other centrally acting agents and thiazide diuretics for hypertensive patients who are elderly, overweight, or diabetic.
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PMID:Endocrinologic effects of antihypertensive therapy with guanabenz or hydrochlorothiazide. 608 24

We have investigated the effects of glucagon and forskolin upon pancreatic islet cell electrical activity using intracellular recordings from single mouse islets. Glucagon (0.1-2.0 microM) and forskolin (0.5-5.0 microM), both adenylate cyclase activators, potentiated glucose (200 mg/dl)-induced electrical activity. In the steady-state, islet cells have cyclic electrical activity with periodically recurring "plateau" depolarizations (with superimposed Ca++ action potentials) separated by silent hyperpolarizations. Both glucagon and forskolin mimicked glucose stimulation by increasing the fraction of each cycle spent in the plateau phase (the "plateau fraction"). Unlike glucose, however, glucagon and forskolin increased, rather than decreased, the overall frequency of plateaus, suggesting that plateau frequency is not tightly linked to changes of plateau fraction. This dissociation was also apparent during the onset of drug action. Plateau fraction increased immediately (within one minute), fell to a nadir and then rose to a new steady state level. Plateau frequency, however, rose slowly and monotonically to a new level. Following drug withdrawal plateau fraction returned to control levels several minutes before plateau fraction. From these results it was concluded that cAMP has two effects upon islet cell electrical activity: one is to increase plateau fraction possibly by stimulating glucose-dependent process, which results in increasing in Ca++ influx, and the other to increase plateau frequency possibly by reducing intracellular Ca++ buffering.
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PMID:Glucagon and forskolin have dual effects upon islet cell electrical activity. 608 71

Glucagon-like peptide-1 (GLP-1), which is an endogenous insulinotropic peptide that can stimulate islet cells to secret insulin, is a promising new drug candidate for the treatment of type 2 diabetes. However, due to the very short half-life of this peptide, the clinical value of GLP-1 is restricted. A GLP-1 peptide analog that had been altered by deletion of five amino acids from the C-terminus (sGLP-1) was selected and investigated in vivo for the therapeutic effect on GK rats with type II DM (T2DM). The results revealed that sGLP-1 exhibited decreased blood glucose-lowering ability compared to GLP-1 in the first week, as measured after once-daily administration. However, after drug administration for 2 weeks, the blood glucose-lowering effect of sGLP-1 became superior to that of GLP-1. sGLP-1 reduced apoptosis of the old islets, enhanced insulin production, and promoted new islets replication. sGLP-1 is a shorter but more efficient GLP-1 analog for type 2 diabetes management. Because sGLP-1 prolonged the proliferation and recovery of islet cells, the ability to maintain blood glucose (BG) within a normal range was still present 2 weeks after drug withdrawal. These results confirmed the importance of the C-terminus of GLP-1 molecule, and further demonstrated that GLP-1 (7-37) can be truncated till the 32nd amino acid to have a better long-term BG lowing function. This result may imply for the presence of glucagon family clearance receptors in vivo and demonstrates that the C-terminus participates in GLP-1 clearance.
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PMID:GLP-1 C-terminal structures affect its blood glucose lowering-function. 1820 Jun 18

Glucagon-like peptide-1 (GLP-1) receptor agonists potentiate glucose-induced insulin secretion. In addition, they have been reported to increase pancreatic beta cell mass in diabetic rodents. However, the precise mode of action of GLP-1 receptor agonists still needs to be elucidated. Here we clarify the effects of the human GLP-1 analog liraglutide on beta cell fate and function by using an inducible Cre/loxP-based pancreatic beta cell tracing system and alloxan-induced diabetic mice. Liraglutide was subcutaneously administered once daily for 30 days. The changes in beta cell mass were examined as well as glucose tolerance and insulin secretion. We found that chronic liraglutide treatment improved glucose tolerance and insulin response to oral glucose load. Thirty-day treatment with liraglutide resulted in a 2-fold higher mass of pancreatic beta cells than that in vehicle group. Liraglutide increased proliferation rate of pancreatic beta cells and prevented beta cells from apoptotic cells death. However, the relative abundance of YFP-labeled beta cells to total beta cells was no different before and after liraglutide treatment, suggesting no or little contribution of neogenesis to the increase in beta cell mass. Liraglutide reduced oxidative stress in pancreatic islet cells of alloxan-induced diabetic mice. Furthermore, the beneficial effects of liraglutide in these mice were maintained two weeks after drug withdrawal. In conclusion, chronic liraglutide treatment improves hyperglycemia by ameliorating beta cell mass and function in alloxan-induced diabetic mice.
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PMID:Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice. 2593 69