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Topic Review
Type 3 Diabetes
The exact connection between Alzheimer’s disease (AD) and type 2 diabetes is still in debate. However, poorly controlled blood sugar may increase the risk of developing Alzheimer’s. This relationship is so strong that some have called Alzheimer’s “diabetes of the brain” or “type 3 diabetes (T3D)”. Given more recent studies continue to indicate evidence linking T3D with AD, this state-of-the-art aimed to demonstrate the relationship between T3D and AD based on the fact that both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are attributed to impaired insulin signaling, and that insulin resistance mediates the dysregulation of bioenergetics and progress to AD. 
  • 5.1K
  • 29 Oct 2020
Topic Review
Type 2 Diabetes: Beta Cell Compensation and Death
Type 2 diabetes (T2D) has become a worldwide epidemic, primarily driven by obesity from overnutrition and sedentariness. Physiologically, T2D manifests as an inability of the pancreatic beta cells to produce and secrete a sufficient bolus of insulin to elicit a response in target cells to transport glucose from the blood and properly regulate glucose levels. Insulin is synthesized in the endoplasmic reticulum (ER) of pancreatic beta cells where it undergoes a series of post-translational modifications to form mature insulin. Insulin resistance requires more insulin to be produced by beta cells to compensate for these desensitized cells. Consequently, this compensation causes additional strain on beta cells. This stress primarily originates from the ER and can also trigger oxidative stress. These cellular stresses can lead to beta cell decompensation, manifested by dysfunction and eventually a loss of beta cell mass.
  • 119
  • 04 Mar 2024
Topic Review
Type 1 Diabetes and Gut Microbiota
Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet β-cells, resulting in a marked loss of β-cell mass and function. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results.
  • 395
  • 07 Dec 2022
Topic Review
Trophectoderm-Specific Knockdown of LIN28
LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy.
  • 853
  • 29 Oct 2020
Topic Review
Trimethylornithine Membrane Lipids
Trimethylornithine membrane lipids (TMOs) are a class of intact polar membrane lipids that were discovered in northern wetland Planctomycete species. The structure of TMOs is similar to ornithine lipids, but the terminal nitrogen of the ornithine amino acid head group is trimethylated, which gives the lipid a charged polar head group.
  • 481
  • 29 Jan 2021
Topic Review
Transcription Factor MAFA in Pancreatic β-cells
MAFA is a basic leucine zipper family transcription factor. In pancreas, MAFA can activate the expression of insulin in β-cells with PDX1 and NEUROD1. MAFA is indeed indispensable for the maintenance of not only insulin expression but also function of adult β-cells. Here, role of MAFA in pancreatic β-cells is mainly described. 
  • 669
  • 13 May 2022
Topic Review
Trans-Endothelial Fatty Acid Transport and Cardiac Metabolism/Contractile
The heart is a metabolic omnivore that combusts a considerable amount of energy substrates, mainly long-chain fatty acids (FAs) and others such as glucose, lactate, ketone bodies, and amino acids. There is emerging evidence that muscle-type continuous capillaries comprise the rate-limiting barrier that regulates FA uptake into cardiomyocytes. The transport of FAs across the capillary endothelium is composed of three major steps—the lipolysis of triglyceride on the luminal side of the endothelium, FA uptake by the plasma membrane, and intracellular FA transport by cytosolic proteins. In the heart, impaired trans-endothelial FA (TEFA) transport causes reduced FA uptake, with a compensatory increase in glucose use. In most cases, mice with reduced FA uptake exhibit preserved cardiac function under unstressed conditions. When the workload is increased, however, the total energy supply relative to its demand (estimated with pool size in the tricarboxylic acid (TCA) cycle) is significantly diminished, resulting in contractile dysfunction. The supplementation of alternative fuels, such as medium-chain FAs and ketone bodies, at least partially restores contractile dysfunction, indicating that energy insufficiency due to reduced FA supply is the predominant cause of cardiac dysfunction. 
  • 358
  • 20 Jan 2022
Topic Review
Timing Sequence and Mechanism of Endocrine Organs Aging
The endocrine glands are one of the most important organs in the context of aging. Failure of the endocrine glands lead to an abnormal hormonal environment, which in turn leads to many age-related diseases. The aging of endocrine glands is closely linked to oxidative stress, cellular autophagy, genetic damage, and hormone secretion. The first endocrine organ to undergo aging is the pineal gland, at around 6 years old. This is followed in order by the hypothalamus, pituitary gland, adrenal glands, gonads, pancreatic islets, and thyroid gland.
  • 406
  • 26 Apr 2023
Topic Review
Time-Restricted Feeding and Weight Loss in Obesity
Across the globe, obesity is a significant concern for public health, a disease characterized by excessive accumulation of body fat, with a negative impact on health. Time-restricted feeding (TRF), in which food accessibility is restricted to a variable period of 8–10 h, especially in the active phase, inducing a prolonged fasting period, is a strategy with potential effects in preventing obesity. Evidence in preclinical studies demonstrated that TRF attenuates the impacts of metabolic disturbances related to high-fat diet feeding in rodents. Through these discoveries, there has been growing interest in revealing the effects associated with TRF in preventing obesity and its comorbidities, as well as investigating its effects in humans. Although TRF is a promising alternative to reduce the impact of obesity, it is necessary to investigate the results on skeletal muscle tissue. Muscle tissue is important for body energy expenditure; however, caloric restriction can negatively impact protein turnover and induce loss of muscle mass, influencing the basal metabolic rate and weight loss.
  • 131
  • 21 Aug 2023
Topic Review
Thyroid Hormone Signaling
Thyroid hormones (TH) perform a plethora of actions in numerous tissues and induce an overall increase in metabolism, with an augmentation in energy demand and oxygen expenditure. Oxidants are required for normal thyroid-cell proliferation, as well as for the synthesis of the main hormones secreted by the thyroid gland, triiodothyronine (T3) and thyroxine (T4). 
  • 343
  • 16 Jun 2023
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