scholarly journals Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6812
Author(s):  
Sabapathy Indu ◽  
Periyasamy Vijayalakshmi ◽  
Jayaraman Selvaraj ◽  
Manikkam Rajalakshmi
Keyword(s):  
Plasma Glucose ◽  
Insulin Signaling ◽  
Plasma Insulin ◽  
Glucose Oxidation ◽  
Stem Bark ◽  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Cassia Fistula ◽  
C Peptide ◽  
Signaling Mechanisms

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p–AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the KATP channel agonist diazoxide

2005 ◽  
Vol 288 (1) ◽  
pp. E80-E85 ◽  
Author(s):  
Bharathi Raju ◽  
Philip E. Cryer
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Temporal Patterns ◽  
Metabolic Responses ◽  
Nonesterified Fatty Acid ◽  
Nonesterified Fatty Acids ◽  
C Peptide

To assess the mechanism, temporal patterns, and magnitudes of the metabolic responses to the ATP-dependent potassium channel agonist diazoxide, neuroendocrine and metabolic responses to intravenous diazoxide (saline, 1.0 and 2.0 mg/kg) and oral diazoxide (placebo, 4.0 and 6.0 mg/kg) were assessed in healthy young adults. Intravenous diazoxide produced rapid, but transient, decrements ( P = 0.0023) in plasma insulin (e.g., nadirs of 2.8 ± 0.5 and 1.8 ± 0.3 μU/ml compared with 7.0 ± 1.0 μU/ml after saline at 4.0–7.5 min) and C-peptide ( P = 0.0228) associated with dose-related increments in plasma glucose ( P = 0.0044) and serum nonesterified fatty acids ( P < 0.0001). After oral diazoxide, plasma insulin appeared to decline, as did C-peptide, again associated with dose-related increments in plasma glucose ( P < 0.0001) and serum nonesterified fatty acids ( P = 0.0141). Plasma glucagon, as well as cortisol and growth hormone, was not altered. Plasma epinephrine increased ( P = 0.0215) slightly only after intravenous diazoxide. There were dose-related increments in plasma norepinephrine ( P = 0.0038 and P = 0.0005, respectively), undoubtedly reflecting a compensatory sympathetic neural response to vasodilation produced by diazoxide, but these would not raise plasma glucose or serum nonesterified fatty acid levels. Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.

scholarly journals Comparison of the Effects of Acarbose and TZQ-F, a New Kind of Traditional Chinese Medicine to Treat Diabetes, Chinese Healthy Volunteers

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Huang Yuhong ◽  
Fu Wenxu ◽  
Li Yanfen ◽  
Liu Yu ◽  
Li Ziqiang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Adverse Events ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Double Blind ◽  
C Peptide ◽  
Treatment Of Diabetes ◽  
Glucose Plasma ◽  
Gastrointestinal Adverse Events

Ethnopharmacological Relevance. TZQ-F has been traditionally used in Traditional Chinese Medicine as a formula for the treatment of diabetes.Aim of the Study. This study aims to compare the pharmacologic effects and gastrointestinal adverse events between TZQ-F and acarbose.Methods. The double-blind randomized placebo-controlled fivefold crossover study was performed in 20 healthy male volunteers. Plasma glucose, plasma IRI, and plasma C-peptide were measured to assess the pharmacologic effects. Flatus and bowel activity were measured to assess the adverse event of gastrointestinal effect.Results. 3 and 4 tablets of TZQ decreased theCmaxof plasma glucose compared with that of the previous day and with placebo. 3 tablets also decreasedCmaxof plasma C-peptide compared with placebo. 4 tablets increasedCmaxof plasma insulin after breakfast and the AUC of plasma C-peptide after breakfast and dinner. 2 tablets did not decrease plasma glucose and elevated theCmaxand AUC of C-peptide after breakfast and dinner, respectively. Acarbose 50 mg decreased theCmaxof plasma insulin and C-peptide after breakfast and theCmaxof plasma glucose and C-peptide after dinner. The subjects who received TZQ did not report any abdominal adverse events.Conclusions. 3 tablets of TZQ have the same effects as the acarbose.

Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia

1981 ◽  
Vol 98 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Ralph A. DeFronzo ◽  
Christian Binder ◽  
John Wahren ◽  
Philip Felig ◽  
Eleuterio Ferrannini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Feedback Inhibition ◽  
Normal Subjects ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Arterial Plasma

Abstract. The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 ± 1 (mean ± sem), 87 ± 15 and 828 ± 210 μU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 ± 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 ± 0.03 pmol/ml at 60 min and 0.14 ± 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 ± 3 μU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

scholarly journals Studies on antidiabetic activity of Acacia ferruginea DC. stem bark

2015 ◽  
Vol 3 (04) ◽  
pp. 11-15
Author(s):  
Jhuma Deb ◽  
Anoop Singh ◽  
Devendra Singh Rathore ◽  
Gouri Kumar Dash ◽  
Nilip Kanti Deb
Keyword(s):  
Amino Acids ◽  
Acute Toxicity ◽  
Methanol Extract ◽  
Blood Glucose Concentration ◽  
Stem Bark ◽  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Standard Drug ◽  
Toxicity Studies ◽  
Phytochemical Studies

The methanol extract of Acacia ferruginea (Family- Mimosaceae) was studied for possible antidiabetic activity on normoglycaemic, OGTT and alloxan induced diabetic rats at doses of 100, 200, and 400 mg/kg, p.o. The acute toxicity studies were carried out on Swiss albino mice to determine the LD50 values. The experiments were performed as per OECD guidelines. The results of the normoglycaemic, OGTT and hyperglycaemic studies revealed that the extract exhibited reduction in blood glucose concentration in a dose dependant manner as compared to the standard drug metformin (250 mg/kg, p.o.). The acute toxicity studies revealed no signs of mortality in animals treated with a single dose of 2000 mg/kg body weight. Preliminary phytochemical studies of the methanol extract revealed presence of alkaloids, steroids, triterpenoids, saponins, flavonoids, tannins and phenolic compounds, carbohydrates, gums and mucilages, proteins and amino acids. The present study justifies the use of the plant for treating diabetes as suggested in folklore remedies.

scholarly journals Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats

2000 ◽  
Vol 164 (1) ◽  
pp. 1-6 ◽  
Author(s):  
CT Musabayane ◽  
O Munjeri ◽  
P Bwititi ◽  
EE Osim
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Plasma Glucose Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Insulin Concentration ◽  
Hydrogel Beads ◽  
Concomitant Reduction

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.

scholarly journals Investigation of the In Vitro Antioxidant Potential Of Polyphenolic-Rich Extract of Artocarpus heterophyllus Lam Stem Bark and Its Antidiabetic Activity In Streptozotocin-Induced Diabetic Rats

2020 ◽  
Vol 25 ◽  
pp. 2515690X2091612 ◽  
Author(s):  
Basiru Olaitan Ajiboye ◽  
Oluwafemi Adeleke Ojo ◽  
Babatunji Emmanuel Oyinloye ◽  
Mary Abiola Okesola ◽  
Adeyonu Oluwatosin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fasting Blood Glucose ◽  
Stem Bark ◽  
Diabetic Rats ◽  
Antioxidant Potential ◽  
Antidiabetic Activity ◽  
Artocarpus Heterophyllus ◽  
Inflammatory Parameters ◽  
Anti Inflammatory

Artocarpus heterophyllus Lam (Moraceae) stem bark has been used locally in managing diabetes mellitus with sparse scientific information. This study investigates the in vitro antioxidant potential of polyphenolic-rich extract of A heterophyllus stem bark as well as its antidiabetic activity in streptozotocin-induced diabetic rats. Fifty male Wistar rats were used with the induction of diabetes by a single intraperitoneal injection of streptozotocin (45 mg/kg body weight) and were orally administered 400 mg/kg free and bound phenols of A heterophyllus stem bark. The animals were sacrificed on the 28th day of the experiment using the cervical dislocation method; antihyperglycemia and anti-inflammatory parameters were subsequently assessed. The polyphenolic extracts demonstrated antioxidant potentials (such as hydrogen peroxide and diphenyl-1-picrylhydrazyl), as well as strong inhibitory activity against amylase and glucosidase. There was a significant ( P < .05) increase in glycogen, insulin concentration, pancreatic β-cell scores (HOMA-β), antioxidant enzymes and hexokinase activities, as well as glucose transporter concentration in diabetic animals administered the extracts and metformin. Also, a significant ( P < .05) reduction in fasting blood glucose, lipid peroxidation, glucose-6-phosphatase, and all anti-inflammatory parameters were observed in diabetic rats administered the extracts and metformin. The extracts demonstrated antidiabetic potential, which may be useful in the management of diabetes mellitus

scholarly journals Beneficial effects of valencene on altered glycoprotein components in streptozotocin-nicotinamide induced diabetic rats

2019 ◽  
Vol 9 (4-A) ◽  
pp. 191-196
Author(s):  
Ellappan Pari ◽  
Pari Leelavinothan ◽  
Thangasamy Gunaseelan ◽  
Duraisamy Kannan
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Experimental Diabetes ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Glycemic Status ◽  
Experimental Diabetes Mellitus ◽  
Citrate Buffer ◽  
Beneficial Effects

ABSTRACT Objective: To investigate the effect of valencene on dearrangement in glycoprotein levels in the streptozotocin(STZ)-nicotinamide(NA)induced diabetic rats. Materials and Methods: Diabetes was induced in experimental rats by a single intraperitoneal (i.p) injection of STZ (45 mg/kg b.w) dissolved in 0.1 M citrate buffer (pH 4.5) 15 minutes after the i.p injection of NA (110 mg/kg b.w). The levels of glycoproteins were altered in experimental diabetes mellitus. Valencene were administered to diabetic rats intragastrically at 100 & 200mg/kg bw for 30days. The effects of valencene on plasma glucose, insulin, plasma and tissue glycoproteins were studied. Results: Oral administration of valencene (200mg/kg b.w)for 30d, dose dependently improved the glycemic status in STZ-NA induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin level. The altered levels of plasma and tissue glycoprotein components were restored to near normal. Conclusions: The results of the present study show the potent beneficial effects of valencene in modifying the levels of glycoprotein components in plasma and tissues of diabetic rats.

scholarly journals Gene expression analysis of hepatic roles in cause and development of diabetes in Goto-Kakizaki rats

2008 ◽  
Vol 200 (3) ◽  
pp. 331-346 ◽  
Author(s):  
Richard R Almon ◽  
Debra C DuBois ◽  
William Lai ◽  
Bai Xue ◽  
Jing Nie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Gene Expression Analysis ◽  
Diabetic Rats ◽  
Β Cell ◽  
Major Consequence ◽  
Chronic Hyperglycemia ◽  
Spontaneously Diabetic Rats ◽  
Wistar Kyoto

Progression of diabetes was studied in male Goto-Kakizaki (GK) spontaneously diabetic rats between 4 and 20 weeks of age, and compared with Wistar-Kyoto (WKY) controls. Five animals from each strain were killed at 4, 8, 12, 16, and 20 weeks of age. Body weight, plasma glucose, and plasma insulin were measured. WKY rats showed a significantly larger weight gain than GK animals from 8 weeks of age onward. Plasma glucose was relatively stable in WKY. By contrast, plasma glucose was higher in GK than WKY even at 4 weeks and continued to increase up to 12 weeks and then maintained a hyperglycemic plateau throughout the remainder of the experiment. Plasma insulin was relatively stable in WKY from 8 weeks onward but was sharply elevated in GK between 4 and 8 weeks. After 8 weeks, insulin declined in GK with GK concentrations lower than WKY at 20 weeks, suggesting β-cell failure. Gene expression in liver was explored using Affymetrix 230-2 gene arrays. Data mining identified 395 probe sets out of more than 31 000 that were differentially regulated. Excluding unidentifiable probe sets and considering duplicate probe sets, there were 311 genes that were expressed differently in the liver of the two strains. A functional analysis of these genes indicated that disruption of lipid metabolism in the liver is a major consequence of the chronic hyperglycemia in the GK strain. In addition, the results suggest that chronic inflammation contributes significantly to the development of diabetes in the GK rats.

THE EFFECT OF RITODRINE ON CARBOHYDRATE AND LIPID METABOLISM IN NORMAL AND DIABETIC PREGNANT WOMEN

1979 ◽  
Vol 92 (4) ◽  
pp. 669-679 ◽  
Author(s):  
Suzan Lenz ◽  
Claus Kühl ◽  
Palle Wang ◽  
Lars Mølsted-Pedersen ◽  
Hans Orskov ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Metabolic Effects ◽  
Plasma Sodium ◽  
C Peptide ◽  
Class A ◽  
Class B

ABSTRACT The metabolic effects of a one hour intravenous infusion of the β-2-receptor stimulating drug ritodrine were studied in seven normal pregnant women, three White class A pregnant diabetics and eight White class B-D pregnant diabetics. During ritodrine infusion all subjects in the three groups exhibited increases in plasma glucose (1.0, 1.6 and 2.1 mmol/l respectively), free fatty acids (360, 850 and 1150 μmol/l), lactate (0.43, 0.80 and 0.86 mmol/l) and β-hydroxybutyrate and decreases in standard bicarbonate. The rise in plasma glucose, free fatty acids and lactate was more pronounced in insulin treated diabetic. The rises in β-hydroxybutyrate and decreases in standard bicarbonate were of the same magnitude in all three groups. Plasma potassium fell in all subjects, whereas no detectable changes in plasma sodium were observed. The endocrine pancreatic function was assessed by measuring plasma insulin (White class A and normals), C-peptide (White class B-D) and glucagon (all subjects). Plasma insulin increased in normals (22 μIU/ml) and White class A diabetics (33 μIU/ml), whereas plasma C-peptide of the insulin treated patients (White class B-D) were below measurable concentrations. Plasma glucagon and cortisol concentrations were not influenced by ritodrine. The results suggest that the diabetogenic changes induced by ritodrine are augmented with the severity of diabetes but not ascribable to a diabetes-like change in the function of the endocrine pancreas.

scholarly journals Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin

1998 ◽  
Vol 274 (5) ◽  
pp. R1482-R1491 ◽  
Author(s):  
Peter J. Havel ◽  
Janet Y. Uriu-Hare ◽  
Tina Liu ◽  
Kimber L. Stanhope ◽  
Judith S. Stern ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Subcutaneous Insulin ◽  
Glucose Lowering ◽  
Streptozotocin Diabetic Rats ◽  
Plasma Leptin

Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg ⋅ kg−1⋅ day−1× 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals ( P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ∼50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose ( P< 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia ( r= −0.64; P < 0.0001) and unrelated to body weight ( P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM ( P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = −63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml ( P< 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering ( r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.

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