Type 1 diabetes patients have often lost all functional beta cells, as indicated by the complete absence of insulin C-peptide from their serum. Pancreatic islet transplantation has been shown to be curative in essence, but is limited by the availability of donor islets, immunological complications and transplant survival. Therefore, attempts to regenerate patient-specific insulin-producing cells have been undertaken using different tissue sources, including embryonal stem cells (ES), induced pluripotent stem cells (iPS), hepatic, exocrine, and alpha cells (Al-Hasani et al., 2013; Collombat et al., 2009; Zhou et al., 2008). In most cases, the approaches to increase beta cell mass have relied on the overexpression of master regulatory transcription factors involved in normal pancreas development, and in only a few cases small molecules or biologicals have been used. Alpha cells are a particularly attractive starting point as they are developmentally closely related to beta cells. These cells have been shown to be able to replenish insulin-producing cell mass following extreme beta cell loss. In a genetic model, overexpression of the transcription factor Pax4 can convert mouse alpha cells to beta cells during development (Collombat et al., 2009) and when triggered in adulthood (Al-Hasani et al., 2013). Molecularly, the beta cell factor Pax4 acts by directly repressing the alpha cell master regulatory transcription factor Arx and loss of Arx alone is sufficient to convert alpha into beta cells (Courtney et al., 2013).
Some antidiabetic treatments employ plant extracts; more than 800 plants have been reported to have antihyperglycemic effects with less adverse effects and low toxicity as compared to synthetic compounds. For example, extraction of aerial parts of Artemisia indica is e.g. described by Ahmad et al. (2014). Major functions of such extracts are found to be based on protective effects of major tissues such as kidney, liver and pancreas.
Artemisinin is a sesquiterpene lactone endoperoxide extracted and isolated from the leaves of Artemisia annua, and well-known as an antimalarial medicine. Artemisinin and its derivatives are described in the WHO monograph on good agricultural and collection practices (GACP) for Artemisia annua L. (WHO monograph 2006).
In a completely different field, namely the field of GABA receptors (i.e. receptors of the gamma-aminobutyric acid, herein called GABAR) which is an ionotropic receptor and ligand-gated ion channel, and its endogenous ligand which is gamma-aminobutyric acid (GABA) the mechanisms of GABAergic synapse formation and plasticity and the role of GABA receptor in the regulation of adult neurogenesis was subject to investigations to understand CNS function (Tyagarajan et al., 2010). Gephyrin is considered a scaffolding molecule of inhibitory synapsis and contributing to GABAR clustering. BTB domain proteins are known to interact with Cullin family ubiquitin ligases and are responsible for targeting specific substrate proteins for ubiquitination and subsequent degradation. (Stogios et al. Genome biology 2005, Genau et al. Mol. Cell 2015). GABA receptors are known to be ubiquitinated (Arancibia-Cárcamo et al. PNAS 2009).
WO 2012/033266 A1 describes specific artemisinin derivatives which are specific glycolipid hybrid derivatives, their antiangiogenic activity and use in preventing and treating angiogenic disease, among them angiogenic disease associated with diabetes.
Davis et al. (Br. J. Clin. Pharmacol. 1997, 44(1):1-7) describe the potential effect of antimalarial drugs on plasma glucose and insulin concentration.
Suresh et al. (International Journal of Pharmaceutical Sciences and Research 2011, 3081) describe phytochemical and pharmacological properties of Artemisia pallens, Walls. Ex DC, commonly known as Davana, an aromatic herb found in India, that has been used for the treatment of diabetes mellitus.
Ahmad et al. (Journal of Ethnopharmacology 2014, 151(1): 618-623) describe antidiabetic activity of Artemisia indica linn (aerial parts) in Streptozotin induced diabetic rats.
Ribnicky et al. (International Journal of Pharmaceutics 2009, 370(1-2):87-92) describe an anti-diabetic extract of Artemisia dracunculus. 
Mannan et al. (Archives of Pharmaceutical Research 2011, 34(10):1657-1661) describe the biosynthesis of artemisinin in several Artemisia species.
WO2014/048788A1 describes the production of pancreatic beta-cells by inhibiting the expression or the activity of Arx in a population of pancreatic alpha-cells.
Suckow et al. (Endocrinology 2008, 149(12):6006-6017) describe the pancreatic beta-cells exocytic machinery and the developmental pathway of beta-cells.
WO2014/007853A1 describes dihydromyricitin for the treatment of diseases and disorders of the glutamatergic system.
USPTO Backgrounds
USPTO Backgrounds