Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates,fats,and protein by promoting the absorption of glucose from the blood into cells of the liver,fat,and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen,via glycogenesis,or fats (triglycerides),via lipogenesis;in the liver,glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone,promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect,promoting widespread catabolism,especially of reserve body fat.
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers:the endothelial cells of the capillary wall,its basement membrane,and between the podocyte foot processes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule,it is processed by the epithelial cells lining the tubule:water is reabsorbed and substances are exchanged;first with the interstitial fluid outside the tubules,and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule,the remaining fluid—urine—exits:it is composed of water,metabolic waste,and toxins.
The connecting peptide,or C-peptide,is a short 31-amino-acid polypeptide that connects insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia,a measurement of C-peptide blood serum levels can be used to distinguish between different conditions with similar clinical features.
Kidney disease,or renal disease,technically referred to as nephropathy,is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure,the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease,where dialysis or a kidney transplant is the only treatment option.
Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix,they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells,based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.
In cell biology,protein kinase C,commonly abbreviated to PKC (EC 2.7.11.13),is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins,or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades.
Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development,or worsening,of many degenerative diseases,such as diabetes,atherosclerosis,chronic kidney disease,and Alzheimer's disease.
Diabetic nephropathy,also known as diabetic kidney disease,is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine,rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive,and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise,the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15,at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.
Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis. It should be distinguished from renovascular hypertension,which is a form of secondary hypertension,and thus has opposite direction of causation.
Diabetic angiopathy is a form of angiopathy associated with diabetic complications. While not exclusive,the two most common forms are diabetic retinopathy and diabetic nephropathy,whose pathophysiologies are largely identical. Other forms of diabetic angiopathy include diabetic neuropathy and diabetic cardiomyopathy.
Upstream stimulatory factor 1 is a protein that in humans is encoded by the USF1 gene.
Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively,a state known as heart failure(HF),with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease,and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.
Mesangial proliferative glomerulonephritis (MesPGN) is a morphological pattern characterized by a numerical increase in mesangial cells and expansion of the extracellular matrix within the mesangium of the glomerulus. The increase in the number of mesangial cells can be diffuse or local and immunoglobulin and/or complement deposition can also occur. MesPGN is associated with a variety of disease processes affecting the glomerulus,though can be idiopathic. The clinical presentation of MesPGN usually consists of hematuria or nephrotic syndrome. Treatment is often consistent with the histologic pattern of and/or disease process contributing to mesangial proliferative glomerulonephritis,and usually involves some form of immunosuppressant.
Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types:acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA),hyperglycemic hyperosmolar state (HHS),lactic acidosis (LA),and hypoglycemia. Chronic complications develop over time and are generally classified in two categories:microvascular and macrovascular. Microvascular complications include neuropathy,nephropathy,and retinopathy;while cardiovascular disease,stroke,and peripheral vascular disease are included in the macrovascular complications.
3-Deoxyglucosone (3DG) is a sugar that is notable because it is a marker for diabetes. 3DG reacts with protein to form advanced glycation end-products (AGEs),which contribute to diseases such as the vascular complications of diabetes,atherosclerosis,hypertension,Alzheimer's disease,inflammation,and aging.
Tumstatin is a protein fragment cleaved from collagen that serves as both an antiangiogenic and proapoptotic agent. It has similar function to canstatin,endostatin,restin,and arresten,which also affect angiogenesis. Angiogenesis is the growth of new blood vessels from pre-existing blood vessels,and is important in tumor growth and metastasis. Angiogenesis is stimulated by many growth factors,the most prevalent of which is vascular endothelial growth factor (VEGF).
In recent years it has become apparent that the environment and underlying mechanisms affect gene expression and the genome outside of the central dogma of biology. It has been found that many epigenetic mechanisms are involved in the regulation and expression of genes such as DNA methylation and chromatin remodeling. These epigenetic mechanisms are believed to be a contributing factor to pathological diseases such as type 2 diabetes. An understanding of the epigenome of diabetes patients may help to elucidate otherwise hidden causes of this disease.
Glomerular hyperfiltration is a situation where the filtration elements in the kidneys called glomeruli produce excessive amounts of pro-urine. It can be part of a number of medical conditions particularly diabetic nephropathy.
SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron,unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium/glucose cotransporter 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control,gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014,several medications of this class had been approved or were under development. In studies on canagliflozin,a member of this class,the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.
IgM nephropathy or immunoglobulin M nephropathy (IgMN) is a kind of idiopathic glomerulonephritis that is marked by IgM diffuse deposits in the glomerular mesangium. IgM nephropathy was initially documented in 1978 by two separate teams of researchers.
