A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in AsiansPark, K.; Chan, J.; Chuang, L.-M.; Suzuki, S.; Araki, E.; Nanjo, K.; Ji, L.; Ng, M.; Nishi, M.; Furuta, H.; Shirotani, T.; Ahn, B.; Chung, S.; Min, H.-K.; Lee, S.; Kim, J.; Cho, Y.; Lee, H.
doi: 10.1007/s00125-008-0933-zpmid: 18251004
The mtDNA 16189C variant is associated with an increased risk of type 2 diabetes in Asians.
Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout miceTsuneki, H.; Murata, S.; Anzawa, Y.; Soeda, Y.; Tokai, E.; Wada, T.; Kimura, I.; Yanagisawa, M.; Sakurai, T.; Sasaoka, T.
doi: 10.1007/s00125-008-0929-8pmid: 18256806
Our results demonstrate a novel role for orexin in hypothalamic insulin signalling, which is likely to be responsible for preventing the development of peripheral insulin resistance with age.
Too much of a good thing: why it is bad to stimulate the beta cell to secrete insulinAston-Mourney, K.; Proietto, J.; Morahan, G.; Andrikopoulos, S.
doi: 10.1007/s00125-008-0930-2pmid: 18246324
In many countries, first- or second-line pharmacological treatment of patients with type 2 diabetes consists of sulfonylureas (such as glibenclamide (known as glyburide in the USA and Canada)), which stimulate the beta cell to secrete insulin. However, emerging evidence suggests that forcing the beta cell to secrete insulin at a time when it is struggling to cope with the demands of obesity and insulin resistance may accelerate its demise. Studies on families with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), the primary defect of which is hypersecretion of insulin, have shown that overt diabetes can develop later in life despite normal insulin sensitivity. In addition, in vitro experiments have suggested that reducing insulin secretion from islets isolated from patients with diabetes can restore insulin pulsatility and improve function. This article will explore the hypothesis that forcing the beta cell to hypersecrete insulin may be counterproductive and lead to dysfunction and death via mechanisms that may involve the endoplasmic reticulum and oxidative stress. We suggest that, in diabetes, therapeutic approaches should be targeted towards relieving the demand on the beta cell to secrete insulin.
Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular diseaseStehouwer, C.; Henry, R.; Ferreira, I.
doi: 10.1007/s00125-007-0918-3pmid: 18239908
Increased arterial stiffness associated with diabetes and the metabolic syndrome may in part explain the increased cardiovascular disease risk observed in these conditions. Arterial stiffness can be estimated by quantifying pulse pressure but is better described by distensibility and compliance coefficients, pulse wave velocity and wave reflection. The most common non-invasive methodologies used to quantify these estimates of arterial stiffness (e.g. ultrasonography and applanation tonometry) are also described. We then review and summarise the current data on the associations between diabetes, the metabolic syndrome and insulin resistance on the one hand and greater arterial stiffness on the other, and identify and discuss some unresolved issues such as differential stiffening of central vs peripheral arterial segments, the impact of sex, and the pathobiology of increased arterial stiffness in diabetes and the metabolic syndrome. Finally, some considerations with regard to treatment options are presented. At present the most powerful therapy available for reducing arterial stiffness is to vigorously treat hypertension using pharmacological agents. New pharmacological strategies to reduce arterial stiffness are likely to be especially relevant to individuals with diabetes.
Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humansKlöting, N.; Schleinitz, D.; Ruschke, K.; Berndt, J.; Fasshauer, M.; Tönjes, A.; Schön, M.; Kovacs, P.; Stumvoll, M.; Blüher, M.
doi: 10.1007/s00125-008-0928-9pmid: 18251005
Expression of adipose tissue FTO mRNA is fat depot-specific and negatively correlates with measures of obesity. However, the direction of this relationship still needs to be elucidated.
Polymorphisms in the TCF7L2 , CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversionKirchhoff, K.; Machicao, F.; Haupt, A.; Schäfer, S.; Tschritter, O.; Staiger, H.; Stefan, N.; Häring, H.-U.; Fritsche, A.
doi: 10.1007/s00125-008-0926-ypmid: 18264689
Diabetes-associated variants in TCF7L2 and CDKAL1 impair insulin secretion and conversion of proinsulin to insulin. However, both aspects of beta cell function are not necessarily linked, as impaired insulin secretion is specifically present in variants of HHEX and impaired proinsulin conversion is specifically present in a variant of SLC30A8 .