Table 1.

Functional heterogeneity observed in human β-cells.

Functional Heterogeneity	Observation	References
Insulin Secretory Response	• Glucose-dependent β-cell recruitment was shown by hemolytic plaque assay	[5]
	• Insulin secretion of β-β and β-α cell pairs was higher than single β-cells
	• A large proportion of non-glucose responding cells secreted insulin in response to other secretagogues
	• In-situ imaging revealed that GIP and GLP-1 recruit a highly coordinated network of β-cells to augment GSIS	[48]
	• β-cells respond to increased glucose concentrations with discrete bursts of insulin secretion	[9]
	• β-cells formed distinct regional clusters of synchronized activity
	• Clusters of β-cells within islets display asynchroneous secretory burst patterns
	• The order in which β-cells show exocytotic responses change over time
	• Glucose-dependent increases in insulin biosynthesis in β-cells	[6]
Calcium Oscillations	• The response was reported to be synchronomous throughout the islet and with the oscillatory pattern modulated by increasing glucose concentrations	[49]
	• Ca2+ signals were observed to be synchronized among β-cells grouped in clusters within the islet, but not to be coordinated throughout the entire β-cell population	[7]
	• Differences in the Ca2+ response were found for cells differentially co-expressing INS and NKX6.1 marker genes	[50]
	• Ca2+ imaging showed β-cell oscillatory activity not to be coordinated throughout the islet. Oscillations were only found when smaller islet regions were analyzed	[8]
	• Computational modeling revealed that β-cell hubs likely dictate the coordinated Ca2+ response in human islets	[51]

Abbreviations: GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; GSIS, glucose stimulated insulin secretion.