. 2018 Sep 10;159(11):3615–3630. doi: 10.1210/en.2018-00705

Table 1.

Involvement of Scaffolds in Cardiometabolic Functions

Scaffold Protein	Model	Modifications	Metabolic Outcome	Reference
β-Arrestin 1	INS1 cells	siRNA knockdown	Impaired GSIS	Sonoda et al. (47)
		Overexpression	Protection from glucose-apoptosis	Quoyer et al. (48)
	Mouse	Systemic knockout	Increased adiposity	Ruderman et al. (49)
			Decreased insulin sensitivity
			Potentiated HFD-induced obesity
	Mouse cardiomyocytes	Overexpression	Resistance to apoptosis	Song et al. (50), Eguchi et al. (51), and Nackiewicz et al. (52)
β-Arrestin-2	Mouse	Liver-specific knockout	Increased gluconeogenesis	Zhu et al. (53)
	Hepatocytes	Overexpression	Decreased gluconeogenesis	Zhu et al. (53)
	Mouse cardiomyocytes	Overexpression	Stress-induced cardiac damage	Eguchi et al. (51)
	Mouse	β-Cell specific knockout	Worsened glucose tolerance after HFD	Zhu et al. (54)
	Mouse	β-Cell specific knockout	GSIS- and KCl-induced insulin secretion reduced	Zhu et al. (54)
		β-Cell overexpression	Enhanced GSIS	Zhu et al. (54)
	Human EndoC-βH1 cells	siRNA knockdown	Impaired GSIS	Zhu et al. (54)
AKAPs	β-Cell	AKAP150 systemic knockout	Impaired insulin secretion	Hinke et al. (55)
			Impacts l-type Ca²⁺currents
			Attenuates cytoplasmic accumulation of Ca²⁺ and cAMP
	Muscle	AKAP150 systemic knockout	Increased insulin sensitivity	Hinke et al. (55)
	Mouse cardiomyocytes	AKAP18α overexpression	Regulate Ca²⁺ influx via PKA in response to β-adrenergic stimulation	Gray et al. (56) and Fraser et al. (57)
		AKAP5 systemic knockout	Impaired trafficking and signaling of β1AR	Klauck et al. (58)
KSR2	C2C12 cells	Expression of KSR2 mutants with human mutations	Reduced glucose oxidation	Pearce et al. (59)
KSR2	C2C12 cells	Expression of KSR2 mutants with human mutations	Increased fatty acid oxidation	Pearce et al. (59)
	Mouse	Systemic knockout	Develops obesity	Liu et al. (60)
			Hyperinsulinemia
			Glucose intolerance
			Increased AMPK-dependent glucose uptake
			Hypophagic
NCK1/2	MIN6 cells	Nck1 knockdown by siRNA	Improves β-cell function	Yamani et al. (61)
NCK1/2	MIN6 cells	Nck1 knockdown by siRNA	Resistance to ER stress	Yamani et al. (61)
	Mouse	Systemic Nck1 knockout	Improves glucose homeostasis	Latreille and Larose (62)
			Enhanced hepatic insulin signaling
			Protects against β-cell apoptosis
	Mouse	Systemic Nck2 knockout	Increased adiposity	Dusseault et al. (63)
14-3-3 Proteins	MIN6 cells	Pharmacological inhibition	Apoptosis	Lim et al. (4)
	Mouse islets	Pharmacological inhibition	Apoptosis	Lim et al. (4)
14-3-3ζ	MIN6 cells	siRNA knockdown	Apoptosis	Lim et al. (4)
	MIN6 cells	Overexpression	Protection from apoptosis	Lim et al. (4)
	3T3-L1 preadipocyte	siRNA knockdown	Inhibition of adipogenesis	Lim et al. (64)
	Mouse	Systemic knockout	Impaired visceral adipogenesis	Lim et al. (64, 65)
			Insulin resistance
			Improved oral glucose tolerance via GLP-1
	Mouse	Systemic overexpression	Enhanced age- and HFD-induced weight gain	Lim et al. (64)
Homer1	Human platelets	Knockdown	Increases TRP channel activity	Jardin et al. (27)
Homer1	Human platelets	Knockdown	Enhanced spontaneous Ca²⁺ influx	Jardin et al. (27)
Caveolin-1	Mouse	Systemic knockout	HFD-induced postprandial hyperinsulinemia	Cohen et al. (33) and Razani et al. (34)
			Decreases insulin sensitivity
			Alterations in lipid homeostasis
			Resistant to HFD-induced obesity
	MIN6 cells	siRNA knockdown	Increases basal insulin secretion	Boothe et al. (35)
	MIN6 cells	siRNA knockdown	Impaired insulin receptor internalization and ERK activation	Nevins et al. (36)
JIP1	INS1 cells	siRNA knockdown	Increases susceptibility to apoptosis	Morel et al. (66)
	Mouse	Systemic knockout	Insulin resistance	Jaeschke et al. (67)

Abbreviations: AMPK, AMP-activated protein kinase; ER, endoplasmic reticulum; GSIS, glucose-induced insulin secretion; HFD, high-fat diet; KSR, kinase suppressor of RAS; Nck, noncatalytic region of tyrosine kinase; siRNA, small interfering RNA.