Insulin effects in muscle and adipose tissue Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia ...
Diabetes research and clinical practice,
08/2011, Letnik:
93
Journal Article
Recenzirano
Abstract The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate ...of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues). These insulin effects serve to encourage the synthesis of carbohydrate, fat and protein, therefore, insulin can be considered to be an anabolic hormone.
ABSTRACT
Impaired wound healing is an important diabetic complication associated with increased morbidity and mortality. It appears to be the net result of micro‐ and macrovascular disease. Diabetic ...neuropathy and the resulting loss of protective sensation (LOPS) has been recognized as one of the major causes for delayed healing in diabetic foot ulcer patients. In addition, hyperglycemia and a number of hyperglycemia‐related factors have been linked to impaired diabetic wound healing, including advanced glycation end products (AGE). A large body of evidence from in vitro and in vivo studies and also data from studies using anti‐AGE agents, indicate that AGE may play a role in the pathogenesis of impaired diabetic wound healing. AGE affect the wound healing process either directly by their interference with a variety of components involved or indirectly through their association with diabetic neuropathy and/or angiopathy. However, further studies need to be performed, mostly clinical studies, to evaluate the exact role of AGE in the impaired diabetic wound healing, suggesting new therapeutic approaches.
The aim of this review is to summarize the effects of vinegar on glucose and lipid metabolism. Several studies have demonstrated that vinegar can help reduce hyperglycemia, hyperinsulinemia, ...hyperlipidemia, and obesity. Other studies, however, have shown no beneficial effect on metabolism. Several mechanisms have been proposed to explain these metabolic effects, including delayed gastric emptying and enteral absorption, suppression of hepatic glucose production, increased glucose utilization, upregulation of flow‐mediated vasodilation, facilitation of insulin secretion, reduction in lipogenesis, increase in lipolysis, stimulation of fecal bile acid excretion, increased satiety, and enhanced energy expenditure. Although some evidence supports the use of vinegar as a complementary treatment in patients with glucose and lipid abnormalities, further large‐scale long‐term trials with impeccable methodology are warranted before definitive health claims can be made.
Hyperthyroidism leads to an enhanced demand for glucose, which is primarily provided by increased rates of hepatic glucose production due to increased gluconeogenesis (in the fasting state) and ...increased Cori cycle activity (in the late postprandial and fasting state). Adipose tissue lipolysis is increased in the fasting state, resulting in increased production of glycerol and nonesterified fatty acids. Under these conditions, increased glycerol generated by lipolysis and increased amino acids generated by proteolysis are used as substrates for gluconeogenesis. Increased nonesterified fatty acid levels are necessary to stimulate gluconeogenesis and provide substrate for oxidation in other tissues (such as muscle). In the postprandial period, insulin-stimulated glucose uptake by the skeletal muscle has been found to be normal or increased, mainly due to increased blood flow. Under hyperthyroid conditions, insulin-stimulated rates of glycogen synthesis in skeletal muscle are decreased, whereas there is a preferential increase in the rates of lactate formation vs. glucose oxidation leading to increased Cori cycle activity. In hyperthyroidism, the Cori cycle could be considered as a large substrate cycle; by maintaining a high flux through it, a dynamic buffer of glucose and lactate is provided, which can be used by other tissues as required. Moreover, lipolysis is rapidly suppressed to normal after the meal to facilitate the disposal of glucose by the insulin-resistant muscle. This ensures the preferential use of glucose when available and helps to preserve fat stores.
Hyperthyroidism leads to an enhanced demand for glucose which is primarily provided by increased rates of hepatic glucose production. In the postprandial period, insulin-stimulated glucose uptake by the skeletal muscle is either normal or increased, mainly due to increased blood flow. Insulin-stimulated rates of glycogen synthesis in skeletal muscle are decreased, whilst there is a preferential increase in the rates of lactate formation versus glucose oxidation leading to increased Cori cycle activity. In the adipose tissue lipolysis is increased in the fasting state, providing non-esterified fatty acids for oxidation in other tissues (such as muscle) and for stimulating gluconeogenesis; however lipolysis quickly subsides after meals to facilitate the disposal of glucose by the insulin resistant muscle.
•Chemerin and leptin are increased, omentin-1 and visfatin are decreased in at term GDM-obese women.•Chemerin and omentin-1 are expressed mainly by the maternal VAT. Leptin is expressed mainly in ...maternal SAT.•Circulating chemerin and leptin in at term pregnancy correlate with BMI and HOMA-IR.•Chemerin and leptin could contribute to insulin resistance and low grade inflammation that characterizes GDM women complicated by obesity.•Weight control during pregnancy is necessary to avoid adverse metabolic complications for the mother and the offspring.
Maternal adipose tissue and the placenta secrete various molecules commonly called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin that are important players in the pathogenesis of insulin resistance. Gestational diabetes mellitus (GDM) is defined as a state of glucose intolerance characterized by β-cell dysfunction and insulin resistance. To examine whether circulating adipokines and their mRNA expression in the adipose tissue and the placenta are altered in GDM pregnancy, we compared 15 GDM women obese (BMI > 30) and non-obese (BMI < 30) to 23 NGT (normal glucose tolerance) women obese and non-obese, at the time of the Cesarean section. Circulating chemerin and leptin were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1, visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p = 0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women. Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1 correlated negatively with BMI. Serum TNF-α was significantly elevated in all obese compared to non-obese pregnant women and correlated positively with BMI. Adiponectin levels were reduced -although not significantly- in GDM- and NGT-obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6 levels did not differ significantly between groups. Chemerin mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was significantly higher compared to placenta in all women (6-to 24-times, p < 0.05). Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and its expression in placenta was negligible in all women. Although, leptin was expressed significantly higher in SAT compared to VAT and the placenta in all women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM and NGT) differed significantly when compared to NGT-non-obese women (3-times higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in GDM women complicated by obesity. This finding together with the positive association of chemerin and leptin with markers of insulin resistance, suggests that these adipokines and more especially chemerin and leptin accompanied by their adipose tissue expression could contribute to the increased insulin resistance and low grade inflammation that characterizes GDM-obese women.
Resistin and the proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to ...the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF-α, IL-6, and IL-1β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF-α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1β production. By comparison, exposure to dexamethasone reduced TNF-α, IL-6, and IL-1β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-α, IL-6, and IL-1β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.
ObjectiveAlthough clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).Design and methodsTo investigate ...this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.ResultsAll three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97±0.22) and SHO (1.99±0.13) versus EU (1.27±0.16, P<0.05), while Matsuda index was decreased in HO (3.89±0.36) and SHO (4.26±0.48) versus EU (7.76±0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 μU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215±19 mean fluorescence intensity, MFI) and SHO (218±24 MFI) versus EU (270±25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481±30 MFI) and SHO (462±19 MFI) were decreased versus EU (571±15 MFI, P=0.04 and 0.004 respectively).ConclusionsIn patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.
Results from landmark diabetes studies have established A1C as the gold standard for assessing long-term glycemic control. However, A1C does not provide "real-time" information about individual ...hyperglycemic or hypoglycemic excursions. Real-time information provided by self-monitoring of blood glucose (SMBG) represents an important adjunct to A1C, because it can differentiate fasting, preprandial, and postprandial hyperglycemia; detect glycemic excursions; identify hypoglycemia; and provide immediate feedback about the effect of food choices, physical activity, and medication on glycemic control. The importance of SMBG is widely appreciated and recommended as a core component of management in patients with type 1 or insulin-treated type 2 diabetes, as well as in diabetic pregnancy, for both women with pregestational type 1 and gestational diabetes. Nevertheless, SMBG in management of non-insulin-treated type 2 diabetic patients continues to be debated. Results from clinical trials are inconclusive, and reviews fail to reach an agreement, mainly because of methodological problems. Carefully designed large-scale studies on diverse patient populations with type 2 diabetes with the follow-up period to investigate long-term effects of SMBG in patients with type 2 diabetes should be carried out to clarify how to make the best use of SMBG, in which patients, and under what conditions.
Thyroid disease in older people Mitrou, Panayota; Raptis, Sotirios A; Dimitriadis, George
Maturitas,
09/2011, Letnik:
70, Številka:
1
Journal Article
Recenzirano
Abstract Several changes in thyroid hormone secretion, metabolism, and action occur with the increase in age. Aging is often associated with a decrease in serum thyroid stimulating hormone and T3 ...levels, whereas serum free T4 levels usually remain unchanged. The prevalence of thyroid dysfunction is higher in the elderly as compared to the younger population. In elderly individuals the non-specific clinical manifestations of thyroid hormone excess or deprivation can cause confusion in the clinical setup; while some of the symptoms of thyroid disease are similar to those in younger patients, it is not uncommon for both hyperthyroidism and hypothyroidism to be manifested in subtle ways in older patients, often mimicking symptoms of aging or masquerading as diseases of the cardiovascular, gastrointestinal, or nervous system. In addition, diagnosis of thyroid disorders is commonly complicated, due to chronic, non-thyroidal illness or medication therapy. Early diagnosis and treatment of overt thyroid disorders is crucial, since these disorders are associated with increased morbidity and mortality in the elderly, usually due to common coexistent diseases such as diminished cardiovascular reserve. Treatment of subclinical thyroid disease should also be considered, based on a combination of age, symptoms and risk factors in the individual patients. In addition, both prevalence and aggressiveness of thyroid cancer increase with age. This review summarizes the changes of thyroid function, as well as the clinical manifestations and treatment of thyroid disorders with advancing age.
Background: Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited.
Methods: To investigate this, a meal was given to 11 ...hypothyroid (HO; aged 45 ± 3 yr) and 10 euthyroid subjects (EU; aged 42 ± 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as (V-A)glycerol(BF)-lipoprotein lipase.
Results: The HO group had higher glucose and insulin levels than the EU group (P < 0.05). In HO vs. EU after meal ingestion (area under curve 0–360 min): 1) BF (1290 ± 79 vs. 1579 ± 106 ml per 100 ml tissue in forearm and 706 ± 105 vs. 1340 ± 144 ml per 100 ml tissue in adipose tissue) and glucose uptake (464 ± 74 vs. 850 ± 155 μmol per 100 ml tissue in forearm and 208 ± 42 vs. 406 ± 47 μmol per 100 ml tissue in adipose tissue) were decreased (P < 0.05), but fractional glucose uptake was similar (28 ± 6 vs. 33 ± 6% per minute in forearm and 17 ± 4 vs. 14 ± 3% per minute in adipose tissue); 2) suppression of lipolysis by insulin was similar; and 3) plasma triglycerides were elevated (489 ± 91 vs. 264 ± 36 nmol/liter·min, P < 0.05), whereas adipose tissue lipoprotein lipase (42 ± 11 vs. 80 ± 21 μmol per 100 ml tissue) and triglyceride clearance (45 ± 10 vs. 109 ± 21 ml per 100 ml tissue) were decreased in HO (P < 0.05).
Conclusions: In hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.
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