The invention provides, in part, methods for diagnosing a pancreatic β-cell disorder, predicting a subject's risk of developing a pancreatic β-cell disorder, monitoring pancreatic β-cell function or pancreatic β-cell mass in a subject at risk of developing a pancreatic β-cell disorder, monitoring efficacy of a treatment of a pancreatic β-cell disorder in a subject, identifying a subject having an increased risk of developing a pancreatic β-cell disorder, selecting a subject for treatment of a pancreatic β-cell disorder, selecting a subject for participation in a clinical study, and detecting endoplasmic reticulum stress in a pancreatic β-cell. These methods include determining at least one level of soluble mesencephalic astrocyte-derived neurotrophic factor (MANF) in a biological sample from the subject. Also provided are pharmaceutical compositions containing a soluble MANF protein and kits containing an antibody or an antigen-binding antibod fragment that binds specifically to a soluble MANF.
