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1.
J Nanosci Nanotechnol ; 6(9-10): 2945-9, 2006.
Article in English | MEDLINE | ID: mdl-17048502

ABSTRACT

There have been several attempts published in the literature related with orally effective insulin formulations, which are increasing in popularity. Some of the results indicate that it is possible to reduce blood glucose level by orally administered liposomal insulin formulations, but there is general need to understand the mechanism and effective components of the liposome formulations. In our study, liposomal insulin formulations were prepared using insulin (Humulin R) or protamine- containing insulin (Humulin N) with cholesterol, dipalmitoyl phosphatidylcholine (egg) (DPPC)-cholesterol mixture, and mucoadhesive agent (methyl cellulose, MC)-added DPPC-cholesterol mixture. A tablet formulation of insulin was also prepared. Formulations of liposomal insulin were introduced to mice and rats orally and reduced blood glucose levels were observed. The composition of phospholipid (DPPC, cholesterol and MC mixture) was found to be quite effective in reducing blood glucose levels. The pH of the solution and the presence of the protamine sulfate were found to be important. The application site was also found to be important because liposomal insulin formulations administered through the mouth or esophagus resulted in reduced blood glucose levels. Reduced blood glucose levels were also observed when tablet formulations of insulin were administered to rats orally.


Subject(s)
Capsules/chemistry , Diabetes Mellitus, Experimental/drug therapy , Insulin/administration & dosage , Insulin/chemistry , Liposomes/chemistry , Nanostructures/chemistry , Administration, Oral , Animals , Blood Glucose/analysis , Chemistry, Pharmaceutical/methods , Diabetes Mellitus, Experimental/blood , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Mice , Rats , Streptozocin , Treatment Outcome
2.
Mol Cell Biochem ; 263(1-2): 143-50, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15524175

ABSTRACT

Patients with chronic diabetes mellitus usually develop reductions in rate and force of cardiac contractions. Since calcium-release channels (ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs)) play integral roles in effecting these processes, we rationalize that alterations in their expression may underlie these defects. To test this hypothesis, right atrial appendages were obtained from diabetic (65.0 +/- 4.5 years) and nondiabetic (56.2 +/- 2.6 years) patients undergoing coronary arterial by-pass grafting and reverse transcription-polymerase chain reactions were used to compare steady state levels of mRNA encoding the three major isoforms of RyRs and IP(3)Rs. In this study we did not detect either RyR1 or RyR3 in human atrial appendage. When compared with nondiabetic patients, mRNA encoding RyR2 from diabetic patients decreased by 74.2 +/- 6.2% (p < 0.01). Diabetes also significantly decreased steady-state levels of mRNA encoding the IP(3)Rs in human atrial appendage. IP(3)R1 decreased by 24.2 +/- 4.6%, IP(3)R2 decreased by 63.0 +/- 4.6% and IP(3)R3 decreased by 55.5 +/- 6.5%. Since a reduction in steady-state mRNA is usually indicative of a decrease in protein levels, these data suggest that the decrease in chronotropy and inotropy seen in chronic diabetic patients may be due in part to a decrease in expression of calcium-release channels.


Subject(s)
Calcium Channels/genetics , Diabetes Mellitus/genetics , Myocardium/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Ryanodine Receptor Calcium Release Channel/genetics , Aged , Base Sequence , Case-Control Studies , Coronary Artery Bypass , DNA, Complementary/genetics , Diabetes Mellitus/metabolism , Diabetes Mellitus/physiopathology , Female , Gene Expression , Heart Atria/metabolism , Heart Rate , Humans , Inositol 1,4,5-Trisphosphate Receptors , Male , Middle Aged , Myocardial Contraction , Reverse Transcriptase Polymerase Chain Reaction
3.
Mol Cell Biochem ; 263(1): 143-50, 2004 Aug.
Article in English | MEDLINE | ID: mdl-27520673

ABSTRACT

Patients with chronic diabetes mellitus usually develop reductions in rate and force of cardiac contractions. Since calcium-release channels (ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs)) play integral roles in effecting these processes, we rationalize that alterations in their expression may underlie these defects. To test this hypothesis, right atrial appendages were obtained from diabetic (65.0 ± 4.5 years) and nondiabetic (56.2 ± 2.6 years) patients undergoing coronary arterial by-pass grafting and reverse transcription-polymerase chain reactions were used to compare steady state levels of mRNA encoding the three major isoforms of RyRs and IP3Rs. In this study we did not detect either RyR1 or RyR3 in human atrial appendage. When compared with nondiabetic patients, mRNA encoding RyR2 from diabetic patients decreased by 74.2 ± 6.2% (p< 0.01). Diabetes also significantly decreased steady-state levels of mRNA encoding the IP3Rs in human atrial appendage. IP3R1 decreased by 24.2 ± 4.6%, IP3R2 decreased by 63.0 ± 4.6% and IP3R3 decreased by 55.5 ± 6.5%. Since a reduction in steady-state mRNA is usually indicative of a decrease in protein levels, these data suggest that the decrease in chronotropy and inotropy seen in chronic diabetic patients may be due in part to a decrease in expression of calcium-release channels. (Mol Cell Biochem 263: 143-150, 2004).

4.
Cardiovasc Diabetol ; 2: 6, 2003 Jun 20.
Article in English | MEDLINE | ID: mdl-12857355

ABSTRACT

BACKGROUND: Using the streptozotocin-induced diabetic rat model, we have recently showed that the expression and function of beta1-adrenoreceptor were decreased in the diabetic rat heart. However, the effect of diabetes on expression of beta-adrenoreceptors in human cardiac tissue remains undefined. Therefore, the focus of the present study was to investigate the effect of diabetes on mRNA encoding beta1- and beta2-ARs in human atrial tissues. METHODS: Right atrial appendages from five diabetic (mean age 65 +/- 4.5; 4 female, 1 male) and five nondiabetic patients (mean age 56.2 +/- 2.8; 4 male, 1 female) undergoing coronary artery bypass grafting were collected and assayed using reverse transcriptase-polymerase chain reaction (RT-PCR) for their mRNA content. No patient from these two groups suffered from acute myocardial infarction and/or failure. All diabetic patients received insulin for at least two years and had been diagnosed as diabetics for at least five years. RESULTS: When compared with levels in nondiabetics, steady state levels of mRNA encoding beta1-adrenoreceptor decreased by 69.2 +/- 7.6% in diabetic patients while beta2-adrenoreceptor mRNA decreased by 32.2 +/- 5.5% (p < 0.001). CONCLUSIONS: Our findings show a decreased expression of beta1- and beta2-adrenoreceptors in human diabetic atrial appendage.

5.
Am J Hypertens ; 15(1 Pt 1): 72-7, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11824864

ABSTRACT

In the present study, we examined the effects of chronic L-arginine treatment on plasma insulin levels and systolic blood pressure (SBP) in fructose-fed (F) rats. Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when compared with that in controls (plasma insulin, 311.3+/-11.4 v control 164.4+/-11.8 pmol/L, P < .05; SBP, 135.4+/-4.2 v control 105.5+/-1.3 mm Hg, P < .05). L-arginine treatment of fructose-hypertensive rats prevented the development of hyperinsulinemia and hypertension (plasma insulin, 200.1+/-7.5 pmol/L; P < .05 compared with that in F rats; SBP, 108.0+/-0.9 mm Hg; P < .05 compared with F rats). However, treatment with L-arginine did not influence any of these parameters in control rats. Statistical analysis of the data of plasma insulin level and SBP, revealed a significant correlation between these two variables. On the other hand, L-arginine treatment of F rats prevented the increased glucose and insulin concentrations in response to oral glucose challenge. L-arginine treatment also prevented the decrease in insulin sensitivity of F rats. These results indicate that L-arginine treatment is able to prevent fructose-induced hypertension and hyperinsulinemia. Our data also suggest a strong relationship between hyperinsulinemia and hypertension in this hypertensive rat model. Therefore, the antihypertensive effect of L-arginine could be, at least in part, the result of the restoration of plasma insulin levels by its vasodilator ability to increase blood flow to insulin sensitive tissues.


Subject(s)
Arginine/pharmacology , Blood Pressure/drug effects , Energy Metabolism/drug effects , Fructose/pharmacology , Hypertension/metabolism , Animals , Blood Glucose/drug effects , Hyperinsulinism/metabolism , Insulin/blood , Insulin Resistance/physiology , Male , Rats , Rats, Sprague-Dawley , Triglycerides/blood
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