. 2011 Nov 9;69(8):1289–1304. doi: 10.1007/s00018-011-0874-4

Table 1.

Phenotypes of selected transgenic mouse models

Transgenic mice		β-cell mass				Metabolic parameters				Pancreas/Islet insulin content	Glucose in ITTⁱ	Susceptibility to exp. diabetes	References
Type	Specificity	Size	Proliferation	Apoptosis	Total mass	Blood glucose		Blood Insulin	In vivo GSIS
Type	Specificity	Size	Proliferation	Apoptosis	Total mass	Fasted/Fed	OGTT/IGTT	Fasted/Fed	OGTT/IGTT
S6K1^−/−	Global	↓	N/D	↔	↓ (endocrine mass)	Fasted: ↔	IGTT: ↑	Fasted: ↓	IGTT: ↓	↓	↓	↓ (HFD)	[116], [165]
S6KCA^RIP	β-cells	↑	↑	↑	↔	Fasted: ↓	IGTT: ↓	Fasted: ↑	IGTT: ↑	N/D	↔	N/D	[39]
rpS6^P−/−	Global	↓	↑	N/D	↔	Fasted/Fed: ↔	IGTT: ↑	Fasted: ↓	N/D	↓	↓	N/D	[131]
4EBP1^−/−	Global	N/D	N/D	N/D	N/D	Fasted/Fed: ↓	N/D	Fed: ↔	N/D	N/D	N/D	N/D	[162]
4EBP1^−/− 4EBP2^−/−	Global	N/D	N/D	N/D	N/D	Fasted: ↔	IGTT: ↔	Fasted: ↑	N/D	N/D	↑	↑ (HFD)	[97]
Rheb (R3/R20^a)	β-cells	↑ (R3)	↔	↔	↑ (R3)	Fed (R20): ↓	OGTT and IGTT (R20): ↓	Fed (R20): ↑	OGTT and IGTT (R20): ↑	N/D	N/D	↓(R3) (STZ)	[63]
βTSC2^−/−b	β-cells; 4–52 weeks	↑	↑	↔	↑ (up to 52 weeks)	Fasted (8-52 weeks)/Fed (4-52 weeks): ↓	IGTT (4,40 and 52 weeks): ↓	Fasted/Fed (4 to 20 weeks): ↑	IGTT (12 weeks): ↑	N/D	N/D	N/D	[123]
	β-cells; ≤35 weeks	↑ (6 weeks)	N/D	↔ (5 weeks)	↑ (6 weeks)	Fed (4-32 weeks): ↓	OGTT (8 weeks): ↓	Fed (12 weeks): ↑	OGTT/IGTT (8 weeks): ↑	N/D	N/D	N/D	[143]
	β-cells; ≥35 weeks	↑ (40 weeks)	N/D	↑ (35 weeks)	↓ (40 weeks)	Fed (36-48 weeks): ↑	N/D	Fed (40-48 weeks): ↓	N/D	N/D	N/D	N/D	[143]
RIP-TSC1cKO	β-cells	↑	↔	↔	↑	Fed: 4 weeks:↓; 8 and 20 weeks: ↔; 12–16 weeks: ↑	IGTT (4 weeks): ↓	Fed (4-24 weeks): ↑	IGTT (4 weeks): ↑	↑	↑ (≥8 weeks)	N/D	[107]
βLKB1KO	β-cells	↑	↑	N/D	↑	Fasted/fed: ↓	IGTT: ↓	Fasted/fed: ↑	IGTT: ↑	↑	↔	↓ (HFD)	[46],[58],[155]
βAMPKDKO	β-cells	↓	↑	↔	↔	Fasted/fed: ↑	IGTT: ↑	Fasted/fed: ↓	IGTT: ↓	N/D	↓	↓ (HFD)	[154]
βAMPK.CA (male)^j	β-cells	↓	N/D	N/D	N/D	Fasted: ↔	IGTT: ↑ (3 months) or ↔ (6 months)	Fasted: ↓ (3 months)	IGTT: ↓ (3 months)	N/D	↔	↔ (HFD)	[154]
βPi3kr1 Pi3kr2DKO	β-cells	N/D	↑	↑	↓	↔	IGTT: ↑	↔	IGTT: ↓	N/D	↔	N/D	[84]
PTEN^+/−	Global	N/D	N/D	N/D	↔	Fasted/fed: ↓	IGTT: ↓	Fasted: ↓	IGTT: ↔	↔	↓	N/D	[174]
RIPcre ⁺ Pten ^fl/fl	β-cells and hypothalamus	↔	↑	↓	↑	Fasted: ↓	IGTT: ↔	Fasted: ↔	N/D	N/D	↓	↓ (STZ)	[152]
RIPcre ⁺ Pten ^fl/fl	β-cells and hypothalamus	↑	↑ (not significant)	↔ but ↓ if STZ treated	↑	Fasted: ↓	IGTT: ↓	Fasted: ↓	IGTT: ↔	↑	↓	↓ (STZ)	[108]
βRicKO^b	β-cells	↔	↓	↔	↓	Fed:↑ (12 and 16 weeks)	IGTT: ↑	N/D	IGTT: ↓	↓	↔	N/D	[59]
Akt1^−/−	Global	N/D	N/D	↑ (testes and thymus)	N/D	Fasted/fed: ↔	OGTT/IGTT: ↔	Fasted: ↔	N/D	N/D	↔	N/D	[25], [27]
RIP-KdAkt	β-cells	↔	N/D	↔	↔	Fasted (4 month): ↔	IGTT (6–8 weeks): ↔	Fasted (4 months): ↔	IGTT (6-8 weeks): ↔	↔	N/D	↑ (HFD)	[10]
RIP-KdAkt	β-cells	↔	N/D	↔	↔	Fed (4 month): ↑	IGTT (6 months): ↑	Fed (4 months): ↓	IGTT (6 months): ↓	↔	N/D	↑ (HFD)	[10]
Myr-Akt1^c	β-cells	↑	↔	↑ but ↓ if STZ treated	↑	Fasted/fed: ↓	IGTT: ↓	Fasted: ↑	IGTT: ↑	↑	↔	↓ (STZ) in reference [163]	[3], [163]
Myr-Akt1^c	β-cells	↑	↑ (5 weeks)	N/D	↑	Fasted/fed: ↔	IGTT: ↓	Fasted: ↑	IGTT: ↑	N/D	N/D	↓ (STZ)	[11]
Myr-Akt1; S6K1^−/−f	β-cells^f	↔^e	↔^e	N/D	N/D	Fasted/fed: ↔^e	IGTT: ↑	Fasted: ↓	N/D	N/D	↓^e	N/D	[3]
Myr-Akt1; S6K1^−/−; S6K2^−/−f	β-cells^f	↓^e	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	N/D	[3]
Akt2^−/−d	Global	N/D	N/D	N/D	↑	Fasted/fed: ↑	OGTT: ↑	↑	N/D	N/D	↑	N/D	[26]
		N/D	N/D	↑^h (24 weeks)	↓^h (24 weeks)	Fasted/fed: ↑	OGTT: ↑ (7 weeks)	↑^g; or ↓ after 8 weeks^h	N/D	↓^h (24 weeks)	↑	N/D	[51]
		N/D	N/D	N/D	N/D	N/D	OGTT: ↑	N/D	N/D	N/D	↑	N/D	[37]
		N/D	N/D	N/D	N/D	Fed: ↔ (6 months)	IGTT: ↑ (6 months)	Fed: ↑ (6 months)	IGTT: ↑ (6 months)	↑	↔	N/D	[24]

↑, increased compared to wild-type; ↓, decreased compared to wild-type; ↔, similar to wild-type; exp., experimental; HFD, high fat diet; GSIS, glucose-stimulated insulin secretion; IGTT, intraperitoneal glucose tolerance test; N/D, no data; OGTT, oral glucose tolerance test; RIP, rat insulin promoter; STZ, streptozotocin

^aRheb over-expression in mouse: R3 and R20 are two independent founder lines used in the study of [63]

^bGlobal deletion of TSC2 or RICTOR causes embryonic lethality [147]

^cMice expressing myristoylated (constitutively active) Akt1

^dPhenotypes of other PKB isoform-combined knock-out mice (Akt1^+/−Akt2^−/−, Akt1^−/−Akt2^+/−, Akt2^−/−Akt3^−/−, Akt1^+/−Akt2^−/−Akt3^−/−, Akt2^−/−Akt3^−/− and others) have also been described [24, 37, 180]. Description of other mouse models related to PKB pathway (e.g., RIP-IGF1, PTEN^−/−, βGSK-3β^−/−, and others) can be found in recent reviews [1, 40]

^eAll parameters (↑, ↓ or ↔) are in comparison to Myr-Akt mice

^fMyr-Akt (beta-cell specific) and S6K1^−/− (and S6K2^−/−) (global deletion) mice were crossed to yield the Myr-Akt;S6K1^−/− (and S6K2^−/−) mice

^gThese Akt2^−/− mice was consistently hyperinsulinemic

^hPlasma insulin levels from these Akt2^−/− mice started to drop after 8 weeks, and they became hypoinsulinemic compared to their wild-type littermates after 24 weeks

ⁱBlood glucose levels during insulin tolerance test (ITT) compared to wild-type animals

^jFemale βAMPK.CA (expressing constitutively active AMPK in β-cells) and βAMPK.DN (expressing dominant negative AMPK in β-cells) mice displayed no abnormalities compared to wild-type in IGTT or ITT