The Role of Insulin Resistance in the Pathogenesis of Diabetes Mellitus

Author(s):  
GERALD M. REAVEN ◽  
JERROLD M. OLEFSKY
Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 125
Author(s):  
Jorge Simón ◽  
Teresa Cardoso Delgado ◽  
Luis Alfonso Martinez-Cruz ◽  
Maria Luz Martínez-Chantar

Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a quarter of the worldwide population. Nevertheless, the development of NASH is often surrounded by a pathological context with other comorbidities, such as cardiovascular diseases, obesity, insulin resistance or type 2 diabetes mellitus. Dietary imbalances are increasingly recognized as the root cause of these NASH-related comorbidities. In this context, a growing concern exists about whether magnesium consumption in the general population is sufficient. Hypomagnesemia is a hallmark of the aforementioned NASH comorbidities, and deficiencies in magnesium are also widely related to the triggering of complications that aggravate NASH or derived pathologies. Moreover, the supplementation of this cation has proved to reduce mortality from hepatic complications. In the present review, the role of magnesium in NASH and related comorbidities has been characterized, unraveling the relevance of maintaining the homeostasis of this cation for the correct functioning of the organism.


2017 ◽  
Vol 06 (04) ◽  
Author(s):  
Soetkin Milbouw ◽  
Julie Verhaegen ◽  
An Verrijken ◽  
Benedicte Y De Winter ◽  
Luc F Van Gaal ◽  
...  

Author(s):  
O. Ye. Pashkova ◽  
N. I. Chudova ◽  
O. S. Litvinenko

The aim — to study the role of myokines in the development of insulin resistance in children with type 1 diabetes mellitus.Materials and methods. Observations involved 68 children with type 1 diabetes mellitus (DM 1), with the mean age 11 to 17 years. Depending on the glycemic controllevel, patients were divided into 3 research groups. The control group consisted of 20 relatively healthy children. Muscle mass, the skeletal muscles index, fat mass and the percentage of fat in the bodywere determined in all patients. The Lovett’s test was used to assess the loss of muscle strength; evaluation of insulin resistance was made based onthe triglyceride­glucose index (TYG). Levels of myostatin, irisin, interleukins ­6 and ­13were measured in blood serum.Results and discussion. It has been established that with deterioration in the level of glycemic controlin DM 1 children, the component redistribution of body composition took place with an increased fat mass proportionand decreased muscle mass. This resulted in the reduced insulin-mediatedabsorption of glucose, that was confirmed by the significant increase in TYG level compared to control group. The analysis of cytokines in the blood serum showed a significant increase in the level of myostatin and interleukin­6 compared with the control group and the tendency to increased levels of the interleukins ­13 and the level of irisin in the blood serum in pediatric patients with DM 1. The increased levels of myostatin in DM 1childrenassociated with an increase in the triglycerides content (r = 0.44, p < 0.05) and raised TYG index (r = 0.33, p < 0.05), testifying theclose correlation between the high myostatin levels and the development of insulin resistance.Conclusions. In children with diabetes mellitus, the reduction of muscle strength and muscle mass take place with a deterioration in the state of glycemic control, accompanying by the development of insulin resistance. The violation of myokines synthesis,along with the chronic hyperglycemia and diabetic myopathy, plays the leading role in the formation of insulin resistance in pediatric patients with DM 1. It is manifested by the increased production of myostatin and interleukin­6 in the absence of activation of irisin and interleukin­13synthesis.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Qiang Wei ◽  
Xiaomin Pu ◽  
Li Zhang ◽  
Yi Xu ◽  
Meifan Duan ◽  
...  

Introduction. The aim of the present study was to examine placental levels of DUSP9 mRNA and protein and to investigate the potential role of DUSP9 in the development of gestational diabetes mellitus (GDM). Methods. Placental tissues from pregnant women with GDM (n=17) and normal healthy pregnant women (n=16) were collected at delivery. The expression of DUSP9 mRNA in placental tissue was analyzed by real-time PCR, while the expression of DUPS9 protein was evaluated by immunohistochemistry and western blot. Differences in the expression levels of DUSP9 mRNA and protein between the two groups were assessed, as well as potential correlations between DUSP9 mRNA expression levels and relevant clinical indicators. Results. Blood glucose levels were significantly higher in the GDM group than in the control group, based on an oral glucose tolerance test. DUSP9 protein was expressed in the placental cytotrophoblasts in both groups, and placental levels of DUSP9 protein and mRNA were significantly higher in women with GDM. Placental DUSP9 mRNA levels in all 33 women correlated moderately with delivery gestational week (R=0.465, P=0.006), fasting plasma glucose (R=0.350, P=0.046), 1-hour postload plasma glucose (R=0.363, P = 0.038), and 2-hour postload plasma glucose (R=0.366, P=0.036), but not with maternal age, preconception body mass index, prenatal body mass index, or neonatal birth weight. Multiple linear regression analysis indicated that delivery gestational week was an influence factor of DUSP9 mRNA levels (β1=0.026, P<0.05). Conclusions. DUSP9 upregulation in the placenta of GDM pregnant women may promote insulin resistance, which may correlate with the occurrence of GDM. But there is still possibility that DUSP9 upregulation was the results of insulin resistance and/or hyperglycemia. Further research is needed to explore the role of DUSP9 in GDM.


2020 ◽  
Vol 21 (19) ◽  
pp. 7246
Author(s):  
Jacek Rysz ◽  
Beata Franczyk ◽  
Janusz Ławiński ◽  
Robert Olszewski ◽  
Anna Gluba-Brzózka

An increasing number of evidence indicates that metabolic factors may play an important role in the development and progression of certain types of cancers, including renal cell carcinoma (RCC). This tumour is the most common kidney cancer which accounts for approximately 3–5% of malignant tumours in adults. Numerous studies indicated that concomitant diseases, including diabetes mellitus (DM) and hypertension, as well as obesity, insulin resistance, and lipid disorders, may also influence the prognosis and cancer-specific overall survival. However, the results of studies concerning the impact of metabolic factors on RCC are controversial. It appears that obesity increases the risk of RCC development; however, it may be a favourable factor in terms of prognosis. Obesity is closely related to insulin resistance and the development of diabetes mellitus type 2 (DM2T) since the adipocytes in visceral tissue secrete substances responsible for insulin resistance, e.g., free fatty acids. Interactions between insulin and insulin-like growth factor (IGF) system appear to be of key importance in the development and progression of RCC; however, the exact role of insulin and IGFs in RCC pathophysiology remains elusive. Studies indicated that diabetes increased the risk of RCC, but it might not alter cancer-related survival. The risk associated with a lipid profile is most mysterious, as numerous studies provided conflicting results. Even though large studies unravelling pathomechanisms involved in cancer growth are required to finally establish the impact of metabolic factors on the development, progression, and prognosis of renal cancers, it seems that the monitoring of health conditions, such as diabetes, low body mass index (BMI), and lipid disorders is of high importance in clear-cell RCC.


2004 ◽  
Vol 89 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Laura Maffei ◽  
Yoko Murata ◽  
Vincenzo Rochira ◽  
Gloria Tubert ◽  
Claudio Aranda ◽  
...  

We present the fourth case of an adult man (29 yr old) affected by aromatase deficiency resulting from a novel homozygous inactivating mutation of the CYP19 (P450arom) gene. At first observation, continuing linear growth, eunuchoid body proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The patient presented also a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, liver steatohepatitis, and signs of precocious atherogenesis. The analysis of the effects induced by the successive treatment with high doses of testosterone, alendronate, and estradiol allows further insight into the roles of androgens and estrogens on several metabolic functions. High doses of testosterone treatment resulted in a severe imbalance in the estradiol to testosterone ratio together with the occurrence of insulin resistance and diabetes mellitus type 2. Estrogen treatment resulted in an improvement of acanthosis nigricans, insulin resistance, and liver steatohepatitis, coupled with a better glycemic control and the disappearance of two carotid plaques. Furthermore, the study confirms previous data concerning the key role of estrogens on male bone maturation, at least in part, and regulation of gonadotropin secretion. The biopsy of the testis showed a pattern of total germ cell depletion that might be due to the concomitant presence of bilateral cryptorchidism. Thus, a possible role of estrogen in male reproductive function is suggested but without revealing a direct cause-effect relationship. Data from this case provide new insights into the role of estrogens in glucose, lipid, and liver metabolism in men. This new case of aromatase deficiency confirms previous data on bone maturation and mineralization, and it reveals a high risk for the precocious development of cardiovascular disease in young aromatase-deficient men.


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