Glucose intolerance in thyrotoxic rats: role of insulin, glucagon, and epinephrine

1988 ◽  
Vol 255 (6) ◽  
pp. E843-E849
Author(s):  
T. Ikeda ◽  
O. Mokuda ◽  
M. Tominaga ◽  
H. Mashiba

To elucidate the possible role of insulin, glucagon, and epinephrine on glucose intolerance in thyrotoxicosis, the secretion of insulin and glucagon in vivo (glucose, arginine, and epinephrine infusion tests) and in perfused pancreas and the hepatic action of insulin, glucagon, and epinephrine in perfused liver were investigated in experimental thyrotoxic rats (induced by thyroxine injection, 20 micrograms/kg sc, for 7 days). In thyrotoxic rats, fasting blood glucose (87 +/- 5 mg/dl, mean +/- SD) and plasma insulin (16 +/- 3 microU/ml) were significantly (P less than 0.001) higher than those in controls (74 +/- 5 mg/dl and 8 +/- 1 microU/ml), respectively. In glucose infusion test (0.5 g/kg iv), blood glucose, plasma insulin, and glucagon responses in thyrotoxic rats were not significantly different from those in controls. In arginine infusion test (5 mg/min for 20 min iv), the increments in blood glucose and plasma insulin after arginine in thyrotoxic rats were not significantly different from those in controls. Plasma glucagon response was almost the same in both groups. In epinephrine infusion test (100 micrograms/kg iv), the increments in blood glucose and plasma insulin in thyrotoxic rats were significantly greater than those in controls. In perfused pancreas, insulin and glucagon secretions in response to 16.7 mM glucose or 6.4 mM arginine in the presence of 5.5 mM glucose in thyrotoxic rats were not different from those in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.


2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.


1990 ◽  
Vol 258 (1) ◽  
pp. E32-E39 ◽  
Author(s):  
S. Klein ◽  
O. B. Holland ◽  
R. R. Wolfe

The importance of the decline in blood glucose concentration on lipolysis and the lipolytic effect of epinephrine was evaluated during short-term fasting. Lipolytic rates were determined by infusing [2H5]glycerol and [1-13C]palmitic acid. Five volunteers were studied after 12 h of fasting before and during epinephrine infusion and after 84 h of fasting, before and during glucose infusion when plasma glucose was restored to postabsorptive values, and during glucose plus epinephrine infusion. In another protocol, five volunteers were given glucose intravenously throughout fasting to maintain plasma glucose at postabsorptive levels and isotopic studies were performed after 12 and 84 h of fasting before and during epinephrine infusion. Glucose infusion after 84 h of fasting restored glucose and insulin concentrations and lipolytic rates toward 12-h fasting values. When euglycemia was maintained throughout fasting, plasma insulin still declined (P less than 0.05) and lipolytic rates still increased (P less than 0.05). Despite similar glucose concentrations, the lipolytic response to epinephrine infusion was greater after 84 h than after 12 h of fasting in both protocols (P less than 0.05). These studies demonstrate that the decline in plasma glucose contributes to, but is not required for, the increase in lipolysis during fasting. The increase in epinephrine-stimulated lipolysis that occurs during fasting is not dependent on a decrease in plasma glucose concentration.


1988 ◽  
Vol 22 (12) ◽  
pp. 969-972 ◽  
Author(s):  
N. Kathryn Lowder ◽  
Henry I. Bussey ◽  
Nancy J. Sugarek

Diuretic-induced glucose intolerance is cited frequently as a problem of only limited clinical significance. In certain populations, such as Mexican-Americans, this effect may be much more dramatic. A 50-year-old obese Mexican-American woman presented with a three-month history of increased thirst and frequent urination. A fasting blood glucose concentration of 365 mg/dL prompted initiation of chlorpropamide therapy. A review of her medical history revealed that a thiazide diuretic was started six months previously. A reduction in thiazide dose and potassium supplementation together with chlorpropamide therapy controlled the patient's blood glucose. Subsequently, all three medications were discontinued, and the patient remained normoglycemic during a full year of follow-up. The temporal relationship between symptomatic diabetes and hydrochlorothiazide therapy incriminates the diuretic as the most probable cause.


2019 ◽  
Vol 35 (4) ◽  
pp. 1398-1406
Author(s):  
Sheryl Joyce B. Grijaldo ◽  
Noel S. Quiming ◽  
Marilou G. Nicolas ◽  
Michael Russelle S. Alvarez

Diabetes mellitus, a complex chronic disease that is associated with hyperglycemia (high blood sugar) affects millions of people worldwide. This study evaluated the hypoglycemic activities of male and female Antidesma bunius, commonly known as currant tree or bignay, extracts in alloxan-treated ICR mice. In addition, the effects of the treatments on blood urea nitrogen (BUN) and creatinine levels were determined. Phytochemical screening using standard protocol was performed. Plant extracts (500 mg/kg) were administered orally via gavage for 14 days and fasting blood glucose (FBG) levels were monitored prior to alloxan-induction on the day of alloxan-induction, and on the 3rd, 7th and 14th days of treatment. Sera were collected on the 14th day to measure the BUN and creatinine levels. Phytochemical screening was performed using standard TLC spray tests. All extracts were found to significantly lower FBG levels compared to the positive (glibenclamide 10 mg/kg) and negative (distilled water) controls (One-way ANOVA, p-value<0.0001). The most active extract, aqueous male A. bunius extract, significantly lowered FBG levels by as much as 61.26±17.89% after the 14th day (paired t-test, p-value = 0.0211). Both BUN and creatinine values were found to be significantly different in the treated mice compared to the controls (One-way ANOVA, p-value = 0.0005 and 0.000479, respectively). The BUN level of all mice was still within normal range, unlike with the creatinine level where only the female and male aqueous A. bunius and female ethanolic A. bunius extracts were within normal range. Phytochemical screening showed the presence of saponins, tannins, and polyphenols, phlobatannins, steroids and terpenoids. This study demonstrates the potential of male and female A. bunius leaf extracts to reduce fasting blood glucose levels. Additional work, pertaining to the identification of possible bioactive compounds and establishing the mechanisms thereof, could be performed.


2021 ◽  
pp. 338-348
Author(s):  
Mizaton Hazizul Hasan ◽  
Hasbullani Zakaria ◽  
Ibtisam Abdul Wahab ◽  
Thellie Ponto ◽  
Aishah Adam

Type 2 diabetes mellitus (T2DM) is one of the main non-communicable chronic diseases that has many complications that compromise the quality of life. Hence, the need to find alternatives to replace the current therapy or as an adjuvant. Tubers of Myrmecodia platytytrea (Rubiaceae) has been used traditionally as an alternative therapy for the management of cancer and other inflammatory-related disorders. The aim of this study was to investigate the potency of M. platytytrea methanolic tuber extract (MPMTE) as an antihyperglycemic agent, in vivo. :The streptozotocin (STZ)-induced diabetic rats were treated orally with MPMTE (100, 200 and 400 mg/kg) and metformin (positive control, 100 mg/kg) daily for 14 days. Blood glucose level and other biochemistry analysis were conducted including histological examination on liver, kidney and pancreas.  The STZ-induced diabetic rats treated with MPMTE (200 and 400 mg/kg) had significant decreased (p<0.05) in fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein (LDL) with no significant changes in high-density lipoprotein (HDL) compared to STZ-induced untreated diabetic rats. Liver, kidney and pancreas were devoid of any damage caused by STZ.  MPMTE had strong antihyperglycaemic activity and was protective against any STZ-induced organ damage. Thus, MPMTE can be further developed into an adjuvant therapy for diabetic patients.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mohamed Akram Melakhessou ◽  
Salah Eddine Marref ◽  
Naima Benkiki ◽  
Cherine Marref ◽  
Imene Becheker ◽  
...  

Abstract Background Diabetes mellitus is a serious complex multifactorial disorder that imposes huge health and economic burden on societies. Because the currently available medications have many drawbacks, it's important to look for alternative therapies. Medicinal plants utilized in folk medicine are ideal candidates. Therefore, this work assessed the antidiabetic action of n-butanol extract from the whole plant Atractylis flava Desf (BEAF). These ethnomedicinal properties of BEAF were scientifically validated using in vitro and in vivo assays. In vitro antidiabetic effect of the BEAF was conducted using α-Glucosidase and α-Amylase assays. While the antihyperglycemic activity was assessed using two rat models: Alloxan-induced diabetic rats and oral glucose challenged rats. Experimental diabetes was induced by a single intraperitoneal injection of alloxan at a dose of 150 mg/kg and animals with fasting blood glucose levels (BGL) > 200 mg/dL were considered diabetic. Glibenclamide (5 mg/kg) was used as a typical drug. Results The BEAF at all tested dose levels (100, 250, and 500 mg/kg) showed a significant decrease in blood glucose level in all the two animal models. Besides, the plant extract exhibited a potent inhibitory effect on α-Amylase and α-Glucosidase activity at a concentration of 1000 µg/mL with 76.17% and 89.37%, respectively. Conclusion BEAF exerts in vitro and in vivo antidiabetic effects, these results suggest that the plant extract can be a therapeutic resource in the treatment of diabetes and hyperlipidemia.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 520
Author(s):  
Soon Yeon Jeong ◽  
Eunjin Kim ◽  
Ming Zhang ◽  
Yun-Seong Lee ◽  
Byeongjun Ji ◽  
...  

The aim of the current study was to examine the antidiabetic effect of noodle containing fermented lettuce extract (FLE) on diabetic mice as a pre-clinical study. The γ-aminobutyric acid (GABA) content, antioxidant capacity, and total polyphenol content of the FLE noodles were analyzed and compared with those of standard noodles. In addition, oral glucose and sucrose tolerance, and fasting blood glucose tests were performed using a high-fat diet/streptozotocin-mediated diabetic mouse model. Serum metabolite profiling of mice feed standard or FLE noodles was performed using gas chromatography–time-of-flight mass spectrometry (GC–TOF-MS) to understand the mechanism changes induced by the FLE noodles. The GABA content, total polyphenols, and antioxidant activity were high in FLE noodles compared with those in the standard noodles. In vivo experiments also showed that mice fed FLE noodles had lower blood glucose levels and insulin resistance than those fed standard noodles. Moreover, glycolysis, purine metabolism, and amino acid metabolism were altered by FLE as determined by GC–TOF-MS-based metabolomics. These results demonstrate that FLE noodles possess significant antidiabetic activity, suggesting the applicability of fermented lettuce extract as a potential food additive for diabetic food products.


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