Celebrating the 100th Anniversary of Insulin's Discovery

In honor of the 100th anniversary of the discovery insulin, the JCI has collected a series of review articles, interviews with prominent scientists, and classic JCI papers reporting seminal findings in diabetes, insulin signaling, and insulin resistance. 

Review series: 100th Anniversary of Insulin's Discovery

Diabetes results from a disturbance in regulating blood sugar. In type 1 diabetes, an autoimmune response triggers the destruction of pancreatic beta cells, which produce insulin that controls glucose uptake in cells, whereas type 2 diabetes is caused by impairments in making or responding to insulin. The discovery of insulin in 1921 led to lifesaving therapy for type 1 diabetes and ushered in the era of modern medicine based on understanding the molecular basis of disease. Curated by JCI’s editor in chief, Rexford S. Ahima, the reviews in this series explore a wide range of topics in diabetes, from insulin’s discovery, insulin secretion and signaling, type 1 diabetes, monogenic diabetes, and insulin resistance syndromes, as well as pharmacological and dietary treatment options for type 2 diabetes. Cumulatively, these reviews highlight the genetic and molecular mechanisms underlying diabetes pathogenesis and discuss existing and potential new therapeutic approaches to treat and manage diabetes.

A personal perspective:

The 2017 Harrington Prize and 2021 Canada Gairdner Award laureates write on the discovery of glucagon-like peptide-1 (GLP-1), an insulin-stimulating glucoregulatory hormone, and GLP-2, and the subsequent translation into transformative therapies.

Related video:

JCI's Conversations with Giants in Medicine: C. Ronald Kahn

Classic articles

Insulin-I131 metabolism in human subjects: demonstration of insulin binding globulin in the circulation of insulin treated subjects

Immunoassay of endogenous plasma insulin in man

Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus

The Significance of Basal Insulin Levels in the Evaluation of the Insulin Response to Glucose in Diabetic and Nondiabetic Subjects

Plasma Insulin Responses to Oral and Intravenous Glucose: Studies in Normal and Diabetic Subjects

Studies of pancreatic alpha cell function in normal and diabetic subjects

The Metabolism of Proinsulin and Insulin by the Liver

Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man

Characterization of antibodies to the insulin receptor: a cause of insulin-resistant diabetes in man

Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose

Characterization of the insulin resistance of aging

Insulin within islets is a physiologic glucagon release inhibitor

C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog

Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus

In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects

Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas

Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp

Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects

Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance

Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance

Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release

Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha

The expression of TNF alpha by human muscle. Relationship to insulin resistance

Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance

Mechanism of free fatty acid-induced insulin resistance in humans

Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR)

Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse

The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus

Insulin resistance differentially affects the PI 3-kinase– and MAP kinase–mediated signaling in human muscle

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

TLR4 links innate immunity and fatty acid–induced insulin resistance

Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients

Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production

Insulin resistance causes inflammation in adipose tissue

Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease

The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity