ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Non-insulin-dependent diabetes mellitus (NIDDM) is a clinically and genetically heterogeneous disorder. Recent advances in molecular genetics have allowed the recognition of the genes involved in some subtypes of NIDDM, Maturity-onset diabetes of the young, an autosomal dominant form of NIDDM, is due to mutations in at least four genes. Recently a maternally transmitted form of diabetes, often associated with deafness, has been shown to be due to mutations in the mitochondrial DNA. Despite these successes, little is known about diabetes susceptibility genes in the common forms of NIDDM. Studies of genes implicated in insulin action or genes involved in insulin secretion have shown associations with insulin resistance (eg, IRS-1) or insulin secretory defects (eg, the glucagon receptor). Studies of other candidate genes, genes mapped in animal models of NIDDM, and a whole genome scan should allow the identification of most diabetes susceptibility genes.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Insulin resistance is a characteristic feature of NIDDM and contributes importantly to the pathophysiology of this disorder. The etiology of insulin resistance in NIDDM is heterogenous, and numerous biochemical defects in the insulin action pathway have been identified in cells from diabetic patients. Because of this complexity, it is difficult to sort out the interactions between genetic and acquired factors. However, one can generally view insulin resistance in NIDDM as consisting of two components; the first is the primary genetic component, and the second is the acquired aspect. Each is due to distinct, but interacting etiologies, and recent advances promise to uncover precise mechanisms of these defects. A number of new developments in this rapidly evolving field are discussed in this review.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and β cell dysfunction. Current research is focused on identifying the genetic or functional abnormalities that cause the glucose intolerance, with the long term goal of designing targeted therapies. This review focuses on the p cell and on what defects occur, when, and why. The genetic basis for typical NIDDM is unknown. Mutations in several rare forms of diabetes have been identified during the past couple of years, including two that affect the β cell: glucokinase mutations in families with maturity-onset diabetes of youth and mitochondrial mutations in persons with maternally inherited diabetes (who often, but not invariably, have deafness). Amyloid deposits are a well-known β-cell anatomic finding in NIDDM. There has been considerable speculation that they cause the hyperglycemia by lowering the mass of functional β cells. The latest information from transgenic mice that overexpress human amylin (the protein that makes up the amyloid deposits) in their β cells is consistent with the amyloid deposition occurring after the onset of hyperglycemia. Many studies have looked at insulin secretion in NIDDM, and two types of abnormalities have been found. Early on, the pulsatile pattern of insulin delivery is disrupted. There is considerable interest in the idea that this defect may hold promise as a way to predict persons at risk for NIDDM, After glucose intolerance begins, β-cell glucose responsiveness becomes impaired, further exacerbating the hyperglycemia. Considerable effort is currently directed at identifying the mechanism for this defect. Multiple possibilities have come from rodent models of NIDDM.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Syndrome X (also referred to as the insulin resistance syndrome or the metabolic disease syndrome) is the association of type II diabetes mellitus with a cluster of other metabolic abnormalities. These include central obesity, hypertension, insulin resistance, hyperinsulinemia, increased plasma triglyceride and decreased high-density lipoprotein cholesterol levels, increased plasma fibrinogen and plasminogen activator inhibitor 1 levels, and microalbuminuria. Individuals with the metabolic disease syndrome have a markedly increased prevalence of macrovascular disease. There are several major questions concerning syndrome X. What is the relationship among the components? Is there a single underlying abnormality, and if so what is it? Are insulin resistance or hyperinsulinemia independent risk factors for cardiovascular disease or hypertension? What is the role of central obesity in syndrome X? The data concerning these issues and a unifying hypothesis are presented.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The glucose transporter isoform CLUT4 is predominantly responsible for insulin-mediated glucose transport in muscle and adipose tissue. The activation of glucose transport is associated with the translocation of GLUT4-containing vesicles from an intracellular pool to the plasma membrane. Much has been learned in the past decade about the changes in the expression of this transporter in insulin-responsive tissues in diabetes mellitus and other insulin-resistant; states. The development of transgenic mice that overexpress CLUT4 or GLUT1 in muscle, adipose tissue, or both has also underscored the importance of the glucose transporters in glucose homeostasis. Data regarding which signaling steps are involved in the activation of glucose transport are just emerging, and even less is known about the molecular and cellular mechanisms governing translocation and recycling of GLUT4 vesicles. Another area of recent interest is the molecular basis of GLUT4 targeting to its intracellular vesicle.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Sulfonylurea agents are effective in lowering blood glucose levels for many years in some patients. Glyburide has active metabolites and a longer half-life than previously described. Combination therapy with a sulfonylurea agent and bedtime NPH insulin appears effective in patients who fail to respond to maximal-dose sulfonylurea agent therapy. Patients with a new onset of type II diabetes and marked hyperglycemia can be safely treated with maximal-dose sulfonylurea agents, avoiding long-term insulin therapy. Although improving glycemic control in patients with type II diabetes may improve the lipid profile, this finding does not appear to be a direct effect of sulfonylurea agents. In an isolated perfused rat pancreas model, glucagon secretion was directly suppressed by sulfonylurea agents. In muscle from patients with type II diabetes, increased expression and content of CLUT-4 was not seen in response to sulfonylurea agents. Finally, muscle glucose oxidation, rather than glucose storage, was increased in response to these drugs. None of these actions of sulfonylurea agents are considered to be their major mechanism of action (which is to increase secretion of insulin).

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Exogenous insulin therapy should be reserved for patients with type II diabetes who have failed other therapeutic modalities, such as dietary manipulation, exercise programs, and maximum doses of oral antidiabetic agents. This paper discusses the current insulin regimens available to normalize glycemia and the glycosylated hemoglobin levels in patients with type II diabetes. In selected patients, combination therapy (daytime oral agents and bedtime intermediate-acting insulin) has been shown to be an effective, safe, and simple technique to normalize glycemia. When combination therapy fails, a split-mixed regimen consisting of an intermediate and regular acting insulin that is split equally between the prebreakfast and predinner meals has been shown to be effective. Single-injection regimens are ineffective in controlling daylong glycemia, and multiple daily injections of insulin do not have significant therapeutic advantages over the easier-to-administer split-mixed regimen. The efficacy and safety of subcutaneous and implantable intraperitoneal insulin pumps will also be discussed. Finally, the benefits of improved glycemia as well as the adverse risks resulting from insulin therapy will be addressed.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Thiazolidinediones are a new class of orally active pharmacological agents that enhance the actions of insulin. These agents increase insulin-dependent glucose disposal and reduce the hepatic glucose output that is commonly elevated in non-insulin-dependent diabetes mellitus. The metabolic changes produced by these drugs result primarily from the increased sensitivity of insulin-sensitive tissues and are observed in numerous animal models of insulin resistance. Although the precise mechanism of action of these drugs remains unknown, transcriptional changes that produce enhanced insulin action are observed in tissue culture cells. Clinical studies are underway to evaluate the safety and effectiveness of thiazolidinediones in non-insulin-dependent diabetes mellitus and in syndromes associated with insulin resistance.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Metformin is the main biguanide drug used in the treatment of type II diabetes. Recent multicenter trials have confirmed the long-term efficacy of this drug in achieving levels of glycemic control comparable with those achieved using sulfonylureas. Metformin acts in a different and complementary manner to sulfonylureas: it reduces insulin resistance without increasing insulin concentrations or causing weight gain. The combination of metformin with a sulfonylurea can confer additive benefits to glycemic control. As the multiple metabolic effects of metformin are further elaborated, the possible use of the drug against obesity, dyslipidemia, and other disorders associated with insulin resistance and hyperinsulinemia continues to attract interest.

ISSN:1068-3097    

出版商:OVID    

年代:1995

数据来源: OVID