Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock‐in, generalized knock‐out and tissue‐specific knockout mice.

Objective-To assess the family history ofdiabetes in non-insulin dependent diabetes mellitus with particular emphasis on parental phenotype.Design-Family histories were obtained from an existing computerised database and supplemented by postal questionnaires.Setting-Diabetic service of a provincial teaching hospital.Subjects-A total of 1326 patients with non-insulin dependent diabetes who had been referred to diabetic clinics over the past 10 years and from whom data had been collected for inclusion in the database, of whom 347 had affected first degree relatives. Nineteen non-white patients were excluded because of the differential hereditability of the disease, and 230 (70%) patients with an affected first degree relative responded to the postal questionnaire.Results-Mothers were implicated in significantly more cases than fathers in patients with a single affected parent: 125 mothers and 48 fathers from database; 82 mothers and 34 fathers from postal questionnaire; p<0 001 in both cases.Conclusions-Maternal influences seem to have an important role in the inheritance of non-insulin dependent diabetes. IntroductionThe genetics of non-insulin dependent diabetes mellitus remains an enigma. It is well known that many patients give a positive family history, but attempts to place the disease into the simple mendelian pattern have failed. Furthermore, molecular genetic studies have not been as successful in finding disease markers as in insulin dependent diabetes.' Several recent studies have suggested that intrauterine environment may also predispose to the development of non-insulin dependent diabetes.2 This would further complicate the transmission pattern of the disease by simulating genetic inheritance through maternal transmission. To clarify the genetics of non-insulin dependent diabetes and the role of maternal inheritance we studied the family history of a large number of patients with noninsulin dependent diabetes.

Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNA(leu(UUR)) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune beta-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena.

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