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Minipig models of diabetes 1 and 2

Minipig models of diabetes 1 and 2 are well characterized and there are many examples of marketed diabetes drugs where the minipig has been used as animal model. 

“Porcine and human insulin differ by only a single amino acid at the 30 position of the B-chain”1

Diabetes

Diabetes mellitus, often just referred to as diabetes, is a group of metabolic diseases characterized by high blood glucose levels because of deficiencies in insulin secretion or insulin action, or both. Diabetes may well have been known as far back as the ancient Egyptians in 1550 BC3 yet it is not until the beginning of the 1900-hundreds treatment became available.

“The porcine pancreas resembles the human pancreas in size, shape, and position.” 1

 Diabetes 1 (DB1) is characterised by pancreatic beta-cell destruction because of an autoimmune response, and can be abrupt in onset and is most often fatal if untreated. Diabetes (DB2) is characterized by insulin resistance and relative insulin deficiency and can have a prolonged onset which may or may not require treatment. Metabolic syndrome is a risk factor for development of DB2. DB1 accounts for 5-10% and DB2 for 90-95% of all cases of diabetes.

Rodent models are used extensively in diabetes research and offer valuable insights into the mechanisms of the disease, but many agree that rodents suffer from poor or limited translatability when it comes to predicting the human situation. This warrants models in larger animals. Many structural and functional similarities of the minipig/human gastrointestinal tract and pancreas coupled with similarities in metabolism and glucose tolerance has made the minipig a strong model in diabetes research1, 4.

Diabetes Type 1

With its abrupt nature and well defined cause, DB1 lends itself better for animal model studies than the more diffuse nature of DB2, and a DB1 model in both pigs and minipigs is well established.

The Göttingen Minipig is widely used in DB1 research1 and has been investigated in detail. Induction of diabetes can be done surgically, by pancreatectomy, however this has wider reaching systemic effects as this procedure completely removes exocrine and endocrine tissue present in the pancreas, and this is not representative of diabetes in man4.

Chemical induction of diabetes can be done using several chemicals; alloxan (ALX), strepozotocin (STZ) and nicotinamide (NIA). Induction of DB1 in the Göttingen Minipig is well described and good reviews have been published1, 5.  Development of auto-antibodies is an important factor in DB1 in humans, but thus far only one case has been published in minipigs2 and a minipig model that displays auto-antibodies present would be a major step forward.

Diabetes Type 2

Because of the complex nature of the disease, predictive animal models of DB2 are few and rare if they exist at all. Because of the prevalence of DB2 in humans this type of Diabetes receives a lot of research attention and literature about DB2 in minipigs can be found in abundance6-12. Different parameters measured in the minipig DB2 model are also published and include insulin secretory capacity and glucose tolerance to assess beta-cell mass2, 6, 11, 13-16. Minipig DB2 models have many of the individual characteristics of DB2, and thus offer a good tool for investigating the underlying mechanisms of DB2.

Case studies

Some insulin drugs have been marketed using the minipig17, 18. In the development of Insulin detemir and liraglutide the minipig has been used as part of the non-rodent safety and efficacy programs.

 

The list of references can provide you with further information about minipig models of Diabetes 1 and 2.