The Effect of Diabetes and Insulin on Liver Glycogen Synthetase Activation

Gold, Alvin H.

doi:10.1016/s0021-9258(18)63353-8

Cited by 132 publications

(9 citation statements)

References 12 publications

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“…In the present study significant increase in fasting and postprandial blood glucose level observed in HFD-STZ induced diabetic animals indicates various possibilities including injury to pancreatic beta cells or reduced peripheral utilization of blood glucose by the target tissues or increased production of glucose by liver cells or increased breakdown of glycogen in the liver [34][35][36]. Decrease in the blood glucose levels as observed in BBR treated groups indicates the role of BBR in improving glycemic control either through pancreatic cells regeneration or by improving the peripheral utilization of glucose as in accordance with earlier studies [37].…”

Section: Discussionmentioning

confidence: 99%

Protective Role of Berberine in Ameliorating Diabetic Complications in Streptozotocin-High Fat Diet Model in Experimental Animals

Bandawane¹,

Mooliya²,

Jadhav³

2020

Int J Pharm Pharm Sci

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Objective: Diabetes mellitus is a serious, complex metabolic disorder and growing health threat disease in the world. Berberine, one of the main constituent in Rhizoma coptidis is widely used in the treatment of diabetes. Potential of berberine in the management of diabetic complications, namely diabetic nephropathy and cardiomyopathy, is however, not yet explored. The present study was, therefore, undertaken to explore the potential of berberine for the management of diabetic nephropathy and diabetic cardiomyopathy in high-fat diet (HFD) and low dose streptozotocin (STZ) induced diabetes in rats. Methods: Rats were fed a high-fat diet for 4 w followed by a single intraperitoneal dose of streptozotocin (35 mg/kg). Animals were divided in five groups. Berberine was given orally in two different dose levels (75 mg/kg and 150 mg/kg) for 28 d. Metformin (100 mg/kg) was used as a standard antidiabetic drug. At the end of the study, parameters evaluated includes glycemic profile, lipid profile, left ventricular indices, urinary protein, serum creatinine, blood urea nitrogen and cardiac antioxidants. Histopathology of kidney and pancreas was carried out. Results: Berberine treated groups showed a significant decrease in fasting blood glucose, glycosylated Hb, creatinine, blood urea nitrogen and urinary total proteins, whereas there was a significant improvement in serum insulin, liver glycogen, skeletal muscle glycogen and cardiac antioxidant enzymes. Conclusion: Present study indicated that berberine shows a protective role in diabetes-associated renal and cardiovascular complications.

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Section: Discussionmentioning

confidence: 99%

Protective Role of Berberine in Ameliorating Diabetic Complications in Streptozotocin-High Fat Diet Model in Experimental Animals

Bandawane¹,

Mooliya²,

Jadhav³

2020

Int J Pharm Pharm Sci

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“…Insulin restores the effect of glucose on glycogen synthetase in diabetic rats (56) and induces, according to Steiner and King (70), the neosynthesis of this enzyme within about 40 min. Insulin also re-establishes the activity of synthetase phosphatase (36) and of the glucokinase (19). The synthesis of this latter enzyme is induced by insulin, but it requires a relatively long time to be achieved; the maximum level is obtained only after 16 and even 48 h (28,61,70).…”

Section: Bernaert Et Al Insulin Effects On Primary Hepatocyte Culturesmentioning

confidence: 99%

Effect of insulin on ultrastructure and glycogenesis in primary cultures of adult rat hepatocytes

Bernaert¹,

Wanson²,

Drochmans³

et al. 1977

The Journal of Cell Biology

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Insulin in the presence of high concentrations of glucose has a beneficial trophic effect on the development of primary cultures of hepatocytes. Compared to the situation observed in hormone-free control cultures, the flattening of the reaggregated hepatocytes is enhanced, and the reconstituted cell trabeculae are enlarged and tend to form a confluent monolayer after 3 days; the survival time is prolonged from 3 to 5 or 6 days. Ultrastructural modifications are also initiated by insulin; numerous glycogen particles appear, after 24 h, in between the cisternae of the proliferated smooth endoplasmic reticulum. After 48 h, large amounts of glycogen are stored, and numerous polysomes are present. A small number of cells show an increased synthesis of lipid droplets in the lumen of the smooth endoplasmic reticulum and form liposomes at the same time. After 72 h, cytolysomes filled with glycogen develop, simulating glycogenosis type II. Simultaneously, microtubules and microfilaments, closely related to numerous polysomes, appear in cytoplasmic extensions constituting undulating membranes.The biochemical data demonstrate that, in the absence of insulin, a high concentration of glucose stimulates glycogenesis and hinders glycogenolysis. This effect of glucose on polysaccharide synthesis is progressively lost. The addition of insulin to the cultures induces, after 48 and 72 h, a three-to fivefold increase of the glucose incorporation into glycogen, as compared to the controls. The presence of insulin is required to maintain the hepatocyte's capacity to store glycogen. Glycogen synthetase is converted into its active form under the influence of glucose. Insulin increases the rate of activation.Primary cultures of hepatocytes isolated from adult rats were used to study the effect of insulin on various metabolic pathways in the liver. As stated by Krahl (48), the primordial function of insulin consists of promoting the formation and storage of macromolecules such as glycogen, lipids, and proteins. Particular efforts were devoted to the study of the effects of insulin on glycogenesis, but contradictory results on the rapid effect of the hormone were obtained during in vivo (6,10,22,24) and in vitro investigations (35,55,64,65). In isolated hepatocytes, the early stimulation of glycogen synthetase and of the synthesis of polysaccharide by insulin has not been demon-

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“…The liver is a vital organ and plays an important role in defending the postprandial hyperglycemia and synthesis of glucose metabolism. The main role of the liver in glucose utilization is to convert the glucose into glucose-6-phosphate with the help of hexokinase, and another role is it converts glucose into energy [ 51 , 52 ]. Alloxan-induced diabetic groups showed an increase in the level of glucose-6-phosphatase, which increased the production of fats to carbohydrates that deposited into the liver and kidneys and thus altered the level of hexokinase, which decreased the conversion and utilization of glucose.…”

Section: Discussionmentioning

confidence: 99%

“…Alloxan-induced diabetic groups showed an increase in the level of glucose-6-phosphatase, which increased the production of fats to carbohydrates that deposited into the liver and kidneys and thus altered the level of hexokinase, which decreased the conversion and utilization of glucose. Another effect of diabetes is an increased level of fructose-1-6-bisphosphatase [ 52 ]. Treating alloxan-induced diabetic groups with different doses of M. africana leaf extract and glibenclamide increased the level of hexokinase and decreased the levels of glucose-6-phosphatase and fructose-1-6-bisphosphatase and brought the levels closer to the levels of normal control.…”

Section: Discussionmentioning

confidence: 99%

Methanolic Extract of Myrsine africana Leaf Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Albino Mice

Amare

2021

Evidence-Based Complementary and Alternative Medicine

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Background. Diabetes mellitus is one of the leading public health problems globally, and its prevalence is increasing in Ethiopia. The current drugs for people with diabetes are costly, less effective, and less safe with a challenging administration method. Thus, globally, the need for alternative herbal antidiabetic medicines is increasing. In the previous studies, antioxidant activities have been seen in crude extracts of M. africana leaves, which is an auspicious sign of antidiabetic property. Accordingly, this study has evaluated the antidiabetic and antidyslipidemic activities of methanolic extract of M. africana leaves. Methods. Hypoglycemic and antihyperglycemic activities of the three doses (250 mg/kg, 500 mg/kg, and 1000 mg/kg) of crude methanolic extract of M. africana leaf were studied on normoglycemic, oral glucose-loaded, and alloxan-induced diabetic mice models. The effect of the extract on diabetic dyslipidemia, insulin and glycated hemoglobin levels, carbohydrate-metabolizing enzymes, and body weight was also studied in alloxan-induced diabetic mice. Glibenclamide (5 mg/kg) was used as a standard drug in all cases. Data analysis was carried out using mixed-design ANOVA. A P value of ≤0.05 was considered a statistically significant difference. Results. The methanolic extract of M. africana leaf did not show acute toxicity up to the dose of 5000 mg/kg and showed better glucose utilization in the oral glucose tolerance test. After 14 days of treatment, M. africana leaf extract decreased the blood glucose level, glycated hemoglobin, glucose-6-phosphatase, and fructose-1-6-bisphosphatase in diabetic mice. In contrast, it increased hexokinase and insulin levels in diabetic mice. Moreover, weight loss and dyslipidemia profiles have been corrected significantly in diabetic mice. Conclusion. M. africana leaves showed antihyperglycemic and antidyslipidemic effects in alloxan-induced diabetic mice. That suggests M. africana may be a potential treatment option for diabetes in the future. However, further molecular studies are required to analyze the mechanisms.

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The Effect of Diabetes and Insulin on Liver Glycogen Synthetase Activation

Cited by 132 publications

References 12 publications

Protective Role of Berberine in Ameliorating Diabetic Complications in Streptozotocin-High Fat Diet Model in Experimental Animals

Protective Role of Berberine in Ameliorating Diabetic Complications in Streptozotocin-High Fat Diet Model in Experimental Animals

Effect of insulin on ultrastructure and glycogenesis in primary cultures of adult rat hepatocytes

Methanolic Extract of Myrsine africana Leaf Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Albino Mice

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