scholarly journals Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1942 ◽  
Author(s):  
Wei Wang ◽  
Daisuke Tanokashira ◽  
Yusuke Fukui ◽  
Megumi Maruyama ◽  
Chiemi Kuroiwa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Animal Models ◽  
Biological Effects ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Serine Phosphorylation ◽  
Memory Decline ◽  
Age Related ◽  
Potential Marker

The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer’s disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in NL-G-F (APPKINL-G-F) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-β (Aβ). Furthermore, we present the first evidence that, in APPKINL-G-F mice showing Aβ42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aβ-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aβ-related memory decline, the modifications of IRS1 may be a marker of early detection of Aβ42 elevation prior to the onset of memory decline in AD.

scholarly journals A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 183
Author(s):  
Anna Izzo ◽  
Elena Massimino ◽  
Gabriele Riccardi ◽  
Giuseppe Della Pepa
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elderly Population ◽  
The Elderly ◽  
Narrative Review ◽  
Macrovascular Complications ◽  
Diabetic Patients ◽  
Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals Spontaneous Type 2 Diabetic Rodent Models

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Health Care ◽  
Animal Models ◽  
Rodent Models ◽  
Advantages And Disadvantages ◽  
Characteristic Features ◽  
Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

Comprehensive Review on Neuro-Degenerative Type 3DM

2021 ◽  
Vol 18 ◽  
Author(s):  
Chandani V. Chandarana ◽  
Salona Roy
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Diabetes Mellitus Type 1 ◽  
Current Data ◽  
The Body ◽  
Type I ◽  
Therapeutic Benefits

: Alzheimer disease (AD) is thought to be the metabolic illness raised by defective insulin signaling, insulin resistance, and low insulin levels in the brain, according to a growing body of research. The "Type 3 diabetes" has been postulated for AD because reduced insulin signalling has molecular and physiological consequences that are comparable to Type I and Type 2 diabetes mellitus (Type 1 DM and Type 2 DM, respectively). The similarities between type 2 diabetes and Alzheimer's disease suggest that these clinical trials might yield therapeutic benefits. However, it's important to note that lowering your risk of Alzheimer's dementia, whether you have diabetes or not, is still a multidimensional process involving factors like exercise, smoking, alcohol, food, and mental challenge. The current aim is to show the relationship between T3D and AD being based on both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are the result of an impaired insulin signaling. The brain's metabolism with its high lipid content and energy needs, places excess demands on mitochondria and appears more susceptible to oxidative damage than the rest of the body. Current data suggests that increased oxidative stress relates to amyloid-β (Aβ) pathology and onset of AD.

scholarly journals Physical exercise prevents the development of type 2 diabetes mellitus in Psammomys obesus

2002 ◽  
Vol 282 (2) ◽  
pp. E370-E375 ◽  
Author(s):  
Yuval Heled ◽  
Yair Shapiro ◽  
Yoav Shani ◽  
Dani S. Moran ◽  
Lea Langzam ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Exercise Training ◽  
Insulin Receptor ◽  
High Energy ◽  
Serine Phosphorylation ◽  
Psammomys Obesus ◽  
Group Protein

We hypothesized that exercise training might prevent diabetes mellitus in Psammomys obesus. Animals were assigned to three groups: high-energy diet (CH), high-energy diet and exercise (EH), and low-energy diet (CL). The EH group ran on a treadmill 5 days/wk, twice a day. After 4 wk, 93% of the CH group were diabetic compared with only 20% of the EH group. There was no difference in weight gain among the groups. Both EH and CH groups were hyperinsulinemic. Epididymal fat (% of body weight) was higher in the CH group than in either the EH and or the CL group. Protein kinase C (PKC)-δ activity and serine phosphorylation were higher in the EH group. No differences were found in tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase among the groups. We demonstrate for the first time that exercise training effectively prevents the progression of diabetes mellitus type 2 in Psammomys obesus. PKC-δ may be involved in the adaptive effects of exercise in skeletal muscles that lead to the prevention of type 2 diabetes mellitus.

scholarly journals ROLE OF YOGA IN ALIENATING THE MEMORY DECLINE AND FRONTAL LOBE METABOLITE CHANGES IN TYPE 2 DIABETES

2016 ◽  
Vol 7 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Rajani Santhakumari ◽  
IndlaYogananda Reddy ◽  
Archana R ◽  
Rajesh P
Keyword(s):  
Type 2 Diabetes ◽  
Frontal Lobe ◽  
Memory Decline
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