Electroacupuncture plus Metformin Lowers Glucose Levels and Facilitates Insulin Sensitivity by Activating Mapk in Steroid-Induced Insulin-Resistant Rats

2015 ◽  
Vol 33 (5) ◽  
pp. 388-394 ◽  
Author(s):  
Hsien-Yin Liao ◽  
Mao-Feng Sun ◽  
Jaung-Geng Lin ◽  
Shih-Liang Chang ◽  
Yu-Chen Lee

Background Type 2 diabetes mellitus is the predominant form of diabetes. Although metformin is the preferred first-line drug for treatment of the disease, it is associated with a risk of secondary failure. Electroacupuncture (EA) can enhance insulin sensitivity and reduce blood glucose levels. Objectives To examine, in an animal study, whether EA combined with metformin (EA–metformin) results in a better glucose-lowering effect and greater insulin sensitivity than metformin alone in steroid-induced insulin-resistant rats. Methods Adult Wistar rats were injected with dexamethasone to induce diabetes and subsequently treated with EA plus metformin or metformin alone. Variations in plasma glucose, plasma insulin, and plasma free fatty acid levels were studied at the midpoint and end of the experimental course. Insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor γ (PPAR-γ), which are associated with glucose transporter type 4 (GLUT4) translocation, and mitogen-activated protein kinase (MAPK), which is related to GLUT4 activation, were measured after EA treatment. Results We found that EA–metformin resulted in a better glucose-lowering effect, greater insulin sensitivity, lower plasma free fatty acid levels and higher levels of MAPK than metformin alone (p<0.05). There were no significant differences between treatment groups in expression of IRS-1 or PPAR-γ. Conclusions The glucose-lowering effect and increased insulin sensitivity associated with EA–metformin administration is governed, at least in part, by its ability to stimulate the activation of GLUT4 via upregulation of MAPK expression.

2018 ◽  
Vol 315 (6) ◽  
pp. E1264-E1273
Author(s):  
Ursula H. Neumann ◽  
Michelle M. Kwon ◽  
Robert K. Baker ◽  
Timothy J. Kieffer

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in β-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.


2020 ◽  
Vol 38 (5) ◽  
pp. 335-342
Author(s):  
Yuan-Chiang Chung ◽  
Ying-I Chen ◽  
Chih-Ming Lin ◽  
Su-Wei Chang ◽  
Tai-Hao Hsu ◽  
...  

Background: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. Methods: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. Results: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (−45% ± 3% vs −19% ± 3%, p < 0.001) and SIIR model rats (−43% ± 2% vs −16% ± 6%, p < 0.001). A significant reduction in plasma FFA levels, improvement in homeostatic model assessment of IR (HOMA-IR) index (−48.9% ± 4.0%, p < 0.001) and insulin sensitivity index (102% ± 16.9%, p < 0.001), and significant increases in insulin receptor substrate 1, glucose transporter 4, and peroxisome proliferator–activated receptor γ protein expressions in skeletal muscle, were also observed in the ACA + EA group of SIIR rats. Conclusion: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.


1977 ◽  
Vol 232 (5) ◽  
pp. E451
Author(s):  
E Hohtola ◽  
R Hissa ◽  
S Saarela

The effects of glucagon injection on temperature regulation and some metabolic parameters were studied in the pigeon. Glucagon (100 microng/kg) always inhibited shivering and caused a fall in the oxygen consumption and body temperature of the unanesthetized pigeon at + 6 degrees C. At + 34 degrees C, the same dose of glucagon had no effect on these parameters. At 22 degrees C, glucagon produced an elevation in plasma free fatty acid (FFA) and blood glucose levels. The rise in FFA at 22 degrees C coincided with the suppression of shivering at 6 degrees C. The glucagon-mediated rise in plasma FFA, but not glucose level, was potentiated by cold ambient temperature. Adrenergic blocking agents given prior to glucagon did not abolish its effects. Phentolamine even prolonged the absence and accelerated the suppression of shivering. A dissociation in the mechanisms by which catecholamines and glucagon suppress shivering is suggested. Although mobilizing energy reserves, glucagon does not seem to be calorigenic in the pigeon at this dose. The interpretation of the changes in plasma FFA levels is discussed in relation to fuel consumption during shivering.


PEDIATRICS ◽  
1969 ◽  
Vol 43 (2) ◽  
pp. 217-225
Author(s):  
Kari O. Raivio ◽  
Kalle Österlund

In a survey of blood glucose levels in 232 erythroblastotic infants during the first 3 days of life, 12 cases of significant hypoglycemia were revealed. Most of these had a severe primary disease; the incidence of hypoglycemia was 17.8% in patients with cord hemoglobin concentrations below 10 gm per 100 ml and 1.9% in those with higher cord hemoglobin levels. The low glucose values were usually observed during the first day of life and were unassociated with recognizable symptoms. Plasma insulin levels, determined in 39 cases before age 24 hours and prior to treatment, were shown to be negatively correlated with the cord hemoglobin concentrations. Hyperinsulinemia, directly correlated with the severity of the erythroblastosis, is postulated to be the cause of the low blood glucose levels. As another consequence of the hyperinsulinemia, a depression of the plasma free fatty acid concentrations was documented. The mechanism of the hyperinsulinemia, the therapeutic and prognostic implications of the hypoglycemia, as well as the effect of the depression of free fatty acid levels on the bilirubin-binding capacity of serum are briefly discussed.


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