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International Journal of Molecular... Oct 2023This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart...
This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. mice heart tissues were compared with mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of mice with decreased levels of mRNA and increased levels of , indicating potential cardiac dysfunction. The mRNA levels of (deubiquitinating enzyme), , and (proteasome β-subunits) were down-regulated in mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in mice, and RNF167 was elevated in diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.
Topics: Mice; Animals; Proteasome Endopeptidase Complex; Ubiquitin; Diabetes Mellitus, Type 2; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Diabetes Complications; RNA, Messenger
PubMed: 37895057
DOI: 10.3390/ijms242015376 -
Cell Metabolism Apr 2021
Topics: Diabetes Mellitus; Glucagon-Like Peptide 1; History, 20th Century; History, 21st Century; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation
PubMed: 33826919
DOI: 10.1016/j.cmet.2021.03.022 -
Journal of Basic and Clinical... Nov 2019Diabetes mellitus (DM) is a group of metabolic diseases related to the dysfunction of insulin, causing hyperglycaemia and life-threatening complications. Current early... (Review)
Review
Diabetes mellitus (DM) is a group of metabolic diseases related to the dysfunction of insulin, causing hyperglycaemia and life-threatening complications. Current early screening and diagnostic tests for DM are based on changes in glucose levels and autoantibody detection. This review evaluates recent studies on biomarker candidates in diagnosing type 1, type 2 and gestational DM based on omics classification, whilst highlighting the relationship of these biomarkers with the development of diabetes, diagnostic accuracy, challenges and future prospects. In addition, it also focuses on possible non-invasive biomarker candidates besides common blood biomarkers.
Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Pregnancy
PubMed: 31730525
DOI: 10.1515/jbcpp-2019-0120 -
Nephron 2021Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and... (Review)
Review
Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.
Topics: Diabetes Mellitus; Humans; Insulin Resistance; Kidney Transplantation; Prediabetic State; Transplant Recipients
PubMed: 33902027
DOI: 10.1159/000514288 -
Physiological Research Jul 2023Chronic venous disease (CVD) is a vascular disorder in which blood return is severely compromised and CVD is usually characterized by venous hypertension. Along with... (Review)
Review
Chronic venous disease (CVD) is a vascular disorder in which blood return is severely compromised and CVD is usually characterized by venous hypertension. Along with obesity and diabetes mellitus, CVD is one of the most common civilization diseases. In general, the estimated prevalence of CVD ranges from 60-80 %. Early diagnosis and adequate treatment are important for preventing progression to more severe stages of the disease like venous leg ulcers. Clinical manifestations of CVD in initial stages of the disease are often asymptomatic. However, as CVD progresses, symptoms begin to develop. Treatment of CVD could be divided into conservative and surgical. Conservative therapy consists of compression, pharmacological treatment and lifestyle change. In cases where conservative therapy is ineffective, surgical or endovascular treatment may be required. The intersections between diabetes mellitus (DM) and CVD are not to be underestimated. CVD and DM have often the same risk factors. Symptoms of CVD can be modified by late complications of DM, but the incidence of different CVD degrees seems to be the same as in diabetics as in non-diabetics population. We are particularly concerned in diabetics about worse compliance with treatment due to their often-poorer adherence to treatment of DM and lifestyle changes. Moreover, there exist a higher risk of CVD and peripheral arterial disease in diabetics patients. Patients with CVD should always be inspected for the presence of DM, considering its presence can have a bearing on CVD symptoms, diagnostic procedures, and therapeutic strategies.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus; Vascular Diseases; Risk Factors; Chronic Disease
PubMed: 37449742
DOI: 10.33549/physiolres.935033 -
Tidsskrift For Den Norske Laegeforening... Apr 2021
Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Guideline Adherence; Humans
PubMed: 33876612
DOI: 10.4045/tidsskr.21.0191 -
Current Diabetes Reports Sep 2019The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk... (Review)
Review
PURPOSE OF REVIEW
The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk of diabetes. This review will examine the latest epidemiological studies linking antipsychotics and diabetes, as well as the mechanisms underlying the association and the clinical implications to minimise the impact of antipsychotics on metabolic health.
RECENT FINDINGS
Although there is an increased risk of diabetes in people with first-episode psychosis, the prevalence increases rapidly after antipsychotics are started. Antipsychotics likely increase the risk of diabetes through weight gain and directly by adversely affecting insulin sensitivity and secretion. It is important to implement measures to prevent diabetes, to screen for diabetes to ensure prompt diagnosis and to provide effective diabetes care. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness.
Topics: Antipsychotic Agents; Diabetes Mellitus; Humans; Insulin Resistance; Psychotic Disorders; Weight Gain
PubMed: 31478094
DOI: 10.1007/s11892-019-1220-8 -
Journal of Diabetes and Its... Nov 2019Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid... (Review)
Review
Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.
Topics: Blood Glucose; Diabetes Complications; Diabetes Mellitus; Gastric Emptying; Gastroparesis; Humans; Hyperglycemia; Postprandial Period; Prognosis; Stomach Diseases
PubMed: 31439470
DOI: 10.1016/j.jdiacomp.2019.107414 -
The Journal of Clinical Endocrinology... May 2022
Topics: Diabetes Mellitus; Gender Identity; Humans; Testosterone; Transgender Persons
PubMed: 35106582
DOI: 10.1210/clinem/dgac060 -
Diabetes Sep 2021The CRISPR/Cas9 genome editing system has been one of the greatest scientific discoveries in the last decade. The highly efficient and precise editing ability of this... (Review)
Review
The CRISPR/Cas9 genome editing system has been one of the greatest scientific discoveries in the last decade. The highly efficient and precise editing ability of this technology is of great therapeutic value and benefits the basic sciences as an advantageous research tool. In recent years, forward genetic screens using CRISPR technology have been widely adopted, with genome-wide or pathway-focused screens leading to important and novel discoveries. CRISPR screens have been used primarily in cancer biology, virology, and basic cell biology, but they have rarely been applied to diabetes research. A potential reason for this is that diabetes-related research can be more complicated, often involving cross talk between multiple organs or cell types. Nevertheless, many questions can still be reduced to the study of a single cell type if assays are carefully designed. Here we review the application of CRISPR screen technology and provide perspective on how it can be used in diabetes research.
Topics: Animals; CRISPR-Cas Systems; Diabetes Mellitus; Gene Editing; Humans; Research
PubMed: 34162685
DOI: 10.2337/dbi20-0047