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Journal Article 2004; 25(6): 403-406 PubMed PMID: 15665799 Citation  Keywords:  Adrenergic alpha-Antagonists:pharmacology, Adrenergic beta-Antagonists:pharmacology, Animals, Diabetes Mellitus, Experimental:drug therapy, Dose-Response Relationship, Drug, Insulin:blood, Islets of Langerhans:drug effects, Male, Oligopeptides:pharmacolog.   

OBJECTIVE: To examine the effect of ipamorelin (IPA), a novel pentapeptide with a strong growth hormone releasing potency, on insulin secretion from pancreatic tissue fragments of normal and diabetic rats.

MATERIALS AND METHODS: Diabetes mellitus was induced by streptozotocin (60 mg kg(-1)). Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were removed and incubated with different concentrations (10(-12) - 10(-6) M) of IPA. Insulin release from the pancreas was measured by radioimmunoassay.

RESULTS: Ipamorelin evoked significant (p<0.04) increases in insulin secretion from the pancreas of normal and diabetic rats. Either diltiazem or yohimbine or propranolol or a combination of atropine, propranolol and yohimbine inhibited IPA-evoked insulin secretion significantly (p<0.03) from the pancreas of normal and diabetic rats. Atropine caused a significant (p<0.007) reduction in the IPA-induced insulin secretion in diabetic but not in normal rats.

CONCLUSION: IPA stimulates insulin release through the calcium channel and the adrenergic receptor pathways. This is the first study to examine the effect of ipamorelin on insulin secretion in the pancreas....

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Journal Article 2004; 25(3): 196-200 PubMed PMID: 15349085 Citation  Keywords:  Acute Disease, Animals, Corticosterone:blood, Encephalomyelitis, Autoimmune, Experimental:blood, Male, Rats, Rats, Wistar, Testosterone:blood, Time Factors,.   

OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) was induced to investigate the levels of circulating total testosterone (TT) and the possible association of corticosterone with the steroid-producing capacity of the testes.

SETTING AND DESIGN: We determined gonad weights, serum TT and corticosterone levels during the development of EAE in male rats.

METHODS: Active EAE was induced in young male Wistar rats by injection of whole myelin in complete Freund's adjuvant. All the rats were weighted and monitored daily for clinical signs and blooded during different phases of the disease. Serum TT was measured by radioimmunoassay and circulating corticosterone was determined using a competitive enzyme immunoassay. Also testes and seminal vesicles were removed to determine their weights.

RESULTS: Seminal vesicle weights and serum TT levels diminished during the acute stage of the disease in all EAE rats and then they began gradually to increase, reaching the normal values at the post-recovery phase. Concomitantly a significant increase in serum corticosterone levels was observed during the acute EAE and the post-recovery phase was accompanied by a decline in corticosterone levels.

MAIN FINDING: Our results indicated an inverse correlation between serum TT and corticosterone levels during the acute EAE. Moreover, the diminution of TT was not a consequence of an alteration of the testes induced by anti-myelin antibodies neither contributed by apoptosis of testis cells by exposure to corticosterone.

CONCLUSIONS: The negative correlation between corticosterone and TT levels associated to EAE may be relevant in understanding the association of the endocrine system and the development of autoimmune demyelinating diseases....

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Journal Article 2002; 23(5-6): 437-439 PubMed PMID: 12500166 Citation  Keywords:  Animals, Diabetes Mellitus, Experimental:chemically induced, Disease Models, Animal, Insulin:pharmacology, Insulin-Like Growth Factor I:analysis, Male, Rats, Rats, Sprague-Dawley, Sulfonylurea Compounds:pharmacology,.   

OBJECTIVE: Diabetes Mellitus is associated with decreased insulin-like growth factor-I (IGF-I) levels and also, poor growth in diabetes is related with low circulating levels of IGF-I. Insulin acts via an increase of IGF-I synthesis on growth. We studied the effects of insulin and sulphonylureas on serum IGF-I levels and aimed to evaluate the restoration of IGF-I in different therapeutic strategies.

DESIGN AND SETTING: Thirty male rats were used in the study and diabetes was induced by a single intraperitoneal injection of streptozotocin (35 mg/kg body weight). After confirmation of hyperglycemia, rats were divided into three groups. The first group was treated with insulin, and second group with glimepiride, third group was not treated (control group). IGF-I levels were measured at basal, after streptozotocin and at the end of the treatment period.

RESULTS: Serum IGF-I levels were found to decrease from 577.2 ng/ml to 253.0 ng/ml after streptozotocin (p<0.005). After 1 month, IGF-1 levels were found 524.0 ng/ml in insulin group, 449.3 ng/ml in sulphonylurea group, and 313.1 ng/ml in control group. The increase in IGF-I was statistically significant in insulin group (p<0.005), and in sulphonylurea group (p<0.05), but it was not significant in control group (p>0.05).

CONCLUSIONS: Serum IGF-I levels decrease in diabetes and insulin treatment restores IGF-I depletion significantly. And although less effective, treatment with glimepiride restores IGF-I levels significantly....

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Journal Article 2002; 23(5-6): 432-436 PubMed PMID: 12500165 Citation  Keywords:  Adrenergic alpha-2 Receptor Antagonists, Adrenergic alpha-Antagonists, Adrenergic beta-Antagonists:pharmacology, Animals, Calcium Channel Blockers:pharmacology, Diabetes Mellitus, Experimental:chemically induced, Disease Models, Animal, Dose-Response Rela.   

OBJECTIVE: Ghrelin is a newly discovered peptide, which was first demonstrated in the epithelium of rat stomach. The purpose of the study was to examine the effect of ghrelin on glucagon secretion from pancreatic tissue fragments of normal and diabetic rats.

METHODS: Diabetes was induced by streptozotocin (60 mg Kg body weight 1) given intraperitoneally. Four weeks after the onset of diabetes, pancreatic fragments of normal and diabetic rats were incubated with different concentrations (10 12 10 6 M) of ghrelin. Glucagon release was measured using radioimmunoassay technique.

RESULTS: Ghrelin failed to stimulate or inhibit glucagon secretion from normal rat pancreas. However, it induced significant increases in glucagon secretion from pancreatic tissue fragments of diabetic rats. Either atropine (muscarinic cholinergic receptor antagonist) or propranolol (beta-adrenergic receptor antagonist) or yohimbine (alpha2-adrenergic receptor antagonist) or diltiazem (calcium channel antagonist) did not affect ghrelin-glucagon interaction. Moreover, a combination of atropine, propranolol and yohimbine had no significant effect on the interaction of ghrelin with glucagon.

CONCLUSION: The ghrelin-induced glucagon secretion in diabetic rats is not controlled via cholinergic or adrenergic pathways. In conclusion, it appears that the main target of ghrelin in the rat endocrine pancreas is not glucagon-producing cells but rather insulin secreting cells which are more involve in weight gain and body growth....

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Journal Article 2002; 23(Suppl 1): 24-29 PubMed PMID: 12019348 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Humans, Melatonin:pharmacology, Neoplasms:drug therapy, Neoplasms, Experimental:drug therapy,.   

: The paper presents the data concerning the in vivo effects of melatonin on experimentally-induced tumors in animals and the in vitro effects on animal and human tumor cells. The majority of experimental tumors responded to the melatonin treatment with growth inhibition. However, some negative or opposite results (i.e. stimulation of tumor instead of inhibition) were also reported. Some of the negative results can be attributed to the improper timing of melatonin administration. Melatonin was also shown to inhibit the growth of several animal and human tumor cell lines in vitro. On the basis of these experiments, a hypothesis of the oncostatic action of melatonin was put forward. The mechanism of the postulated action is complex and probably includes: 1) modulation of the endocrine system; 2) modulation of the immune system; 3) the direct oncostatic action of melatonin on tumor cells. The latter includes the recently discovered anti-oxidative action which probably plays an important role in the countering the DNA damage during the radiation challenge or the exposure to chemical carcinogens. It also includes the antiproliferative and pro-apoptotic effects exerted via melatonin receptors expressed by tumor cells. The involvement of the membrane melatonin receptors is mainly assumed. However, the recent data from our and other laboratories suggest also the involvement of RZR/ROR receptors (the putative melatonin nuclear receptors) in both melatonin-induced proliferation inhibition and apoptosis....

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Journal Article 2001; 22(6): 441-447 PubMed PMID: 11781542 Citation  Keywords:  Age Factors, Animals, Antioxidants:pharmacology, Female, Gene Expression Regulation, Neoplastic:drug effects, Mammary Neoplasms, Experimental:drug therapy, Melatonin:pharmacology, Mice, Mice, Transgenic, Photoperiod, RNA, Messenger:analysis, Receptor, Erb.   

OBJECTIVES AND DESIGN: The effect and the mechanism of light regimen and melatonin on the development of mammary tumors in HER2/neu transgenic mice were investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen (LD) or constant light illumination (LL) and a part of each group was given melatonin (20 mg/l) during the night time.

RESULTS: The exposure to LL failed to change the incidence of spontaneous mammary adenocarcinoma development, the size of mammary tumors, as well as the incidence and size of lung metastases. However, the number of tumors per mouse was significantly increased in the LL group as compared to the LD group. The number of mice bearing 4 and more tumors was higher in the LL group than in the LD group, whereas the number of mice bearing 1 to 3 tumors was lower in the LL group in comparison with the LD group. Melatonin decreased the incidence and size of mammary adenocarcinomas, and the incidence of lung metastases in the LD group but not in the LL group. The mean number of tumors per mouse was not changed by melatonin treatment in both light regimens. The number of mice bearing 4 and more tumors was reduced by melatonin more significantly in the LL group than in LD group. Melatonin treatment resulted in a 2.5-fold reduction in the expression of HER-2/neu mRNA in mammary tumors from HER-2 /neu transgenic mice.

CONCLUSION: The data demonstrate the influence of the LD light regiment and melatonin treatment in the development of spontaneous mammary tumors in HER-2/neu mice suggesting a melatonin-dependent modulation of HER-2/neu gene expression in mammary adenocarcinoma....

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Journal Article 2001; 22(4): 238-242 PubMed PMID: 11524629 Citation  Keywords:  Animals, Blood Glucose:analysis, Cholesterol:blood, Diabetes Mellitus, Experimental:metabolism, Hydrolases:metabolism, Insulin:blood, Kidney:enzymology, Liver:enzymology, Lysosomes:enzymology, Male, Rabbits,.   

OBJECTIVES: The study was carried out on fifty male rabbits of the New Zealand White breed. Diabetes was caused by a single, intravenous alloxan injection. Rabbits which had glycaemia 7th day after the alloxan administration higher than 11 millimol/litre were selected for the studies. They were divided into 5 groups: I - control (without diabetes); II - 3-week diabetes; III - 6-week diabetes; IV - 3-month diabetes; V - 6-month diabetes.

METHODS: In control and experimental rabbits the activity of beta-glucuronidase, N-acetyl-beta-glucosaminidase, lysosomal acid phosphatase, leucine aminopeptidase, cathepsin D, and lysosomal arylesterase was determined in lysosomal fractions of the liver and kidney.

RESULTS: Alloxan caused lowering of the activity of all the investigated enzymes in the kidney and liver except lysosomal arylesterase.

CONCLUSION: Alloxan injection caused a significant increase in the activity of all the investigated enzymes. The advisable lysosomal enzymes may be useful for the monitoring of the course and effectiveness of diabetes therapy....

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